Materiały źródłowe

• #1 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  Bile reflux occurs when bile a digestive liquid produced in your liver backs up (refluxes) into your stomach and, in some cases, into the tube that connects your mouth and stomach (esophagus). […] Unlike gastric acid reflux, bile reflux can’t be completely controlled by changes in diet or lifestyle. Treatment involves medications or, in severe cases, surgery. […] In cases of bile reflux, the valve doesn’t close properly, and bile washes back into the stomach. This can lead to inflammation of the stomach lining (bile reflux gastritis). […] Bile and stomach acid can reflux into the esophagus when another muscular valve, the lower esophageal sphincter, doesn’t work properly. […] Bile reflux may be caused by: […] Stomach surgery, including total or partial removal of the stomach and gastric bypass surgery for weight loss, is responsible for most bile reflux.

• #2 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #3 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. […] However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. […] The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. […] Increasing evidence has demonstrated that bile reflux is thought to be associated with atrophic gastritis, IM, dysplasia, and even carcinogenesis. […] The mechanism of bile acid-induced gastric IM in the stomach is not clear and needs further research. […] Bile reflux, also known as duodenogastric reflux, refers to the backflow of duodenal contents, including bile, pancreatic juice, and duodenal juice, into the stomach.

• #4 Bile reflux after bariatric surgery | Cirugía Española (English Edition)

  https://www.elsevier.es/es-revista-cirugia-espanola-english-edition–436-articulo-bile-reflux-after-bariatric-surgery-S2173507723002235

  The growing epidemic of obesity and the increase in weight loss surgery has led to a resurgence of interest in biliary reflux because anatomical alterations may be refluxogenic. […] Although obesity is an independent risk factor for the development of gastro-oesophageal reflux, the anatomical alterations of bariatric surgery may also be refluxogenic. Duodenal contents (bile, bicarbonate and pancreatic enzymes) may reflux into the stomach and oesophagus, which is called duodenogastro-oesophageal reflux (DGOR) or biliary reflux. […] It is well documented that bile acids, together with gastric acid, contribute to reflux-type symptoms (heartburn, regurgitation, etc.), erosive oesophagitis and Barrett’s oesophagus. […] Patients with more advanced oesophageal lesions have a higher degree of duodenal reflux than those with simpler lesions. It has been demonstrated in animal models and in vitro that there is more Barrett’s and dysplasia with duodenal reflux.

• #5 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #6 Biliary reflux – Wikipedia

  https://en.wikipedia.org/wiki/Biliary_reflux

  Biliary reflux, also called bile reflux, duodenogastroesophageal reflux (DGER) or duodenogastric reflux, is a condition that occurs when bile and/or other contents like bicarbonate and pancreatic enzymes flow upward (refluxes) from the duodenum into the stomach and esophagus. […] Bile is a digestive fluid made by the liver, stored in the gallbladder, and discharged into the duodenum after food is ingested to aid in the digestion of fat. Normally, the pyloric sphincter prevents bile from entering the stomach. When the pyloric sphincter is damaged or fails to work correctly, bile can enter the stomach and then be transported into the esophagus as in gastric reflux. The presence of small amounts of bile in the stomach is relatively common and usually asymptomatic, but excessive refluxed bile causes irritation and inflammation.

• #7 Bile Reflux: Symptoms, Treatment, Causes & What It Is

  https://my.clevelandclinic.org/health/diseases/22056-bile-reflux

  Bile reflux occurs when the valves that keep bile from backwashing into your stomach and esophagus arent working properly. Bile can erode the delicate linings of your stomach and esophagus, causing inflammation and tissue damage. […] Bile reflux occurs when bile from the small intestine backwashes into the stomach, and sometimes into the esophagus. Bile refluxes from the small intestine into the stomach and esophagus. […] Normally, everything involved in the digestive process should only flow one way down. As food progresses along the digestive tract, valves at the end of each organ open just enough to let food and digestive juices through into the next, without letting anything flow back the other way. But if these valves (sphincters) arent functioning right, reflux can happen, and digestive juices like bile can flow back into organs where they dont belong.

• #8 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  Bile reflux occurs when bile a digestive liquid produced in your liver backs up (refluxes) into your stomach and, in some cases, into the tube that connects your mouth and stomach (esophagus). […] Unlike gastric acid reflux, bile reflux can’t be completely controlled by changes in diet or lifestyle. Treatment involves medications or, in severe cases, surgery. […] In cases of bile reflux, the valve doesn’t close properly, and bile washes back into the stomach. This can lead to inflammation of the stomach lining (bile reflux gastritis). […] Bile and stomach acid can reflux into the esophagus when another muscular valve, the lower esophageal sphincter, doesn’t work properly. […] Bile reflux may be caused by: […] Stomach surgery, including total or partial removal of the stomach and gastric bypass surgery for weight loss, is responsible for most bile reflux.

• #9 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #10 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #11 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/journal/view.html?spage=400&volume=27&number=3

  Bile reflux gastropathy is associated with functional dyspepsia and causes more severe symptoms. […] Cholecystectomy predisposes to BG and abnormal pain, and could contribute to the pathogenesis of functional dyspepsia. […] The pathoetiology of functional dyspepsia remains unclear; one mechanism could be chemical gastropathy from chronic bile reflux. […] Gastric luminal irritants include the reflux of duodenal contents into the stomach such as bile salts, alkaline pancreatic, and duodenal secretions, lysolecithin, or ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). […] Cholecystectomy may serve as a risk factor for bile reflux into the stomach. […] Prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance.

• #12 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  Bile reflux occurs when bile a digestive liquid produced in your liver backs up (refluxes) into your stomach and, in some cases, into the tube that connects your mouth and stomach (esophagus). […] Unlike gastric acid reflux, bile reflux can’t be completely controlled by changes in diet or lifestyle. Treatment involves medications or, in severe cases, surgery. […] In cases of bile reflux, the valve doesn’t close properly, and bile washes back into the stomach. This can lead to inflammation of the stomach lining (bile reflux gastritis). […] Bile and stomach acid can reflux into the esophagus when another muscular valve, the lower esophageal sphincter, doesn’t work properly. […] Bile reflux may be caused by: […] Stomach surgery, including total or partial removal of the stomach and gastric bypass surgery for weight loss, is responsible for most bile reflux.

• #13 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #14 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  When bile reflux occurs, secondary bile acids and free bile acids are regurgitated into the stomach. […] Bile acids inhibit the activity of NO enzyme and the sodium hydrogen exchange of cells, leading to intracellular DNA damage, apoptosis, and mutation. […] Bile reflux can stimulate gastrin secretion from G cells, which promotes gastric acid secretion and inhibits pyloric sphincter contraction, further promoting bile reflux and forming a vicious circle. […] Recent studies have shown that acidic bile acids in gastric juice after successful Hp eradication can also induce mucosal dysfunction with changes in the microRNA (miRNA) profile, which might drive the development of gastric carcinogenesis. […] Investigating bile acid-induced IM is important and necessary for the prevention of GC.

• #15 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #16 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #17 Richard John Torrens Medical blogs – Bile reflux

  http://med.torrens.org/gord/bile.php

  Having experienced bile reflux myself I can make a few comments about it. Unlike acid reflux – which can be easily controlled by PPIs or antacids, there is no medically effective remedy for bile reflux, so the doctors simply aren’t interested – which is disgraceful as bile reflux is often caused by PPIs. Furthermore bile reflux is difficult to distinguish from acid reflux. However an understanding of the bile system and how it goes wrong can give some pointers. […] Gastric bile is strongly implicated as a cause of stomach cancer and in the formation of Barrett’s oesophagus, hence progression to oesophageal adenocarcinoma. The removal of the gallbladder will cause constant bile release into the pylorus when it may well get into the stomach. […] The digestive system is hugely complicated: there are many known hormones – Gastrin, Secretin, Cholecystokinin, Ghrelin, Motilin – and probably more to be discovered. They interact with stomach acidity in ways that are still being explored.

• #18 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  Bile reflux occurs when bile a digestive liquid produced in your liver backs up (refluxes) into your stomach and, in some cases, into the tube that connects your mouth and stomach (esophagus). […] Unlike gastric acid reflux, bile reflux can’t be completely controlled by changes in diet or lifestyle. Treatment involves medications or, in severe cases, surgery. […] In cases of bile reflux, the valve doesn’t close properly, and bile washes back into the stomach. This can lead to inflammation of the stomach lining (bile reflux gastritis). […] Bile and stomach acid can reflux into the esophagus when another muscular valve, the lower esophageal sphincter, doesn’t work properly. […] Bile reflux may be caused by: […] Stomach surgery, including total or partial removal of the stomach and gastric bypass surgery for weight loss, is responsible for most bile reflux.

• #19 Bile reflux: Symptoms, causes, treatment and more

  https://www.medicalnewstoday.com/articles/bile-reflux

  Bile reflux occurs when bile, a liquid that the liver makes, flows back up into the stomach or the esophagus. It may be a sign of an underlying condition or a complication of certain surgical procedures. […] Bile reflux can also occur as a side effect of certain surgical treatments, for example, gastric or gallbladder surgery. […] When one of the valves, or sphincters, that usually prevent digestive fluids from going in the wrong direction is not functioning properly, it can cause bile reflux. Bile ends up in places in the body it should not be. […] Bile reflux tends to be uncommon in people who do not have any health problems, but it is a well-known complication of certain surgeries. […] Bile reflux differs from acid reflux, which occurs when the gastric acids flow back into the esophagus.

• #20 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  Bile reflux occurs when bile a digestive liquid produced in your liver backs up (refluxes) into your stomach and, in some cases, into the tube that connects your mouth and stomach (esophagus). […] Unlike gastric acid reflux, bile reflux can’t be completely controlled by changes in diet or lifestyle. Treatment involves medications or, in severe cases, surgery. […] In cases of bile reflux, the valve doesn’t close properly, and bile washes back into the stomach. This can lead to inflammation of the stomach lining (bile reflux gastritis). […] Bile and stomach acid can reflux into the esophagus when another muscular valve, the lower esophageal sphincter, doesn’t work properly. […] Bile reflux may be caused by: […] Stomach surgery, including total or partial removal of the stomach and gastric bypass surgery for weight loss, is responsible for most bile reflux.

• #21 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  A peptic ulcer can block the pyloric valve so that it doesn’t open or close properly. […] People who have had their gallbladders removed have significantly more bile reflux than do people who haven’t had this surgery. […] Bile reflux gastritis has been linked to stomach cancer. […] The combination of bile reflux and acid reflux also increases the risk of the following complications: […] Bile is often suspected of contributing to GERD when people respond incompletely or not at all to powerful acid-suppressant medications. […] Animal studies have also linked bile reflux to Barrett’s esophagus. […] In animal studies, bile reflux alone has been shown to cause cancer of the esophagus.

• #22

  https://link.springer.com/article/10.1007/BF02212691

  To establish the pathogenic role of duodenogastric reflux in dyspeptic symptoms we have compared the clinical features, gastrointestinal motility, and rates of duodenogastric bile reflux in 12 cholecistectomized dyspeptic patients, 12 dyspeptic patients with intact gallbladder, and 12 healthy controls. […] Fasting gastric bile acid concentrations were higher in cholecystectomized patients (P0.05) and antral postcibal motility lower (P0.05) than in the other groups. […] We concluded that patients with functional dyspepsia and a prior cholecystectomy have clinical features similar to those with gallbladders, but some physiological features are dissimilar: antral motility is decreased and duodenogastric bile reflux is increased.

• #23 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  A peptic ulcer can block the pyloric valve so that it doesn’t open or close properly. […] People who have had their gallbladders removed have significantly more bile reflux than do people who haven’t had this surgery. […] Bile reflux gastritis has been linked to stomach cancer. […] The combination of bile reflux and acid reflux also increases the risk of the following complications: […] Bile is often suspected of contributing to GERD when people respond incompletely or not at all to powerful acid-suppressant medications. […] Animal studies have also linked bile reflux to Barrett’s esophagus. […] In animal studies, bile reflux alone has been shown to cause cancer of the esophagus.

• #24 Bile Reflux: Clinical Considerations – Gastroenterology Advisor

  https://www.gastroenterologyadvisor.com/features/tips-for-distinguishing-and-treating-biliary-reflux/

  Bile reflux occurs when the bile secreted into the duodenum moves retrograde into the stomach and potentially into the esophagus. […] In certain patients with bile reflux, it has been postulated that a weak or widely patent pylorus could predispose patients to this condition. […] Bile reflux may also be more common in patients with motility disorders, especially in those whose gastric or duodenal motility is reduced, including certain patients with type 2 diabetes mellitus or those taking chronic opioid medications. […] Patients who have undergone gastric surgeries where the pylorus is bypassed or disrupted may be predisposed to developing bile reflux as well. […] Bile reflux is typically alkaline in nature, compared with the acidic environment found in the stomach. […] Despite this difference in pH, patients can experience similar symptoms, making bile reflux and GERD difficult to distinguish.

• #25

  https://link.springer.com/article/10.1007/s00534-008-0010-5

  The sphincter of Oddi is located at the distal end of the pancreatic and bile ducts; it regulates the outflow of bile and pancreatic juice. […] Therefore, in these patients, two-way regurgitation (pancreatobiliary and biliopancreatic reflux) occurs. This results in various pathological conditions of the biliary tract and the pancreas. Biliopancreatic reflux could be confirmed by: operative or postoperative T-tube cholangiography; CT combined with drip infusion cholangiography; histological detection of gallbladder cancer cells in the main pancreatic duct; and reflux of bile on the cut surface of the pancreas. […] Although the true prevalence, degree, and pathophysiology of biliopancreatic reflux remain unclear, biliopancreatic reflux is related to the occurrence of acute pancreatitis. […] Even if no obstruction is present, biliopancreatic reflux can still result in acute pancreatitis in some cases.

• #26 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #27 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #28 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36134174/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] Besides, researches have established that BRG is closely associated with the development of precancerous lesions and gastric cancer. […] Inflammation (hyperemia, edema, erosion) stimulation of bile acids, lysolecithin, and so on. […] In this review, we briefly evaluate this disorder based on the best available evidence, offering an overview of its complicated pathogenesis, diverse relevant factors, potential carcinomatous risk, modern diagnostic investigations, and effective therapeutic plans.

• #29 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #30 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #31 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  When bile reflux occurs, secondary bile acids and free bile acids are regurgitated into the stomach. […] Bile acids inhibit the activity of NO enzyme and the sodium hydrogen exchange of cells, leading to intracellular DNA damage, apoptosis, and mutation. […] Bile reflux can stimulate gastrin secretion from G cells, which promotes gastric acid secretion and inhibits pyloric sphincter contraction, further promoting bile reflux and forming a vicious circle. […] Recent studies have shown that acidic bile acids in gastric juice after successful Hp eradication can also induce mucosal dysfunction with changes in the microRNA (miRNA) profile, which might drive the development of gastric carcinogenesis. […] Investigating bile acid-induced IM is important and necessary for the prevention of GC.

• #32 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  When bile reflux occurs, secondary bile acids and free bile acids are regurgitated into the stomach. […] Bile acids inhibit the activity of NO enzyme and the sodium hydrogen exchange of cells, leading to intracellular DNA damage, apoptosis, and mutation. […] Bile reflux can stimulate gastrin secretion from G cells, which promotes gastric acid secretion and inhibits pyloric sphincter contraction, further promoting bile reflux and forming a vicious circle. […] Recent studies have shown that acidic bile acids in gastric juice after successful Hp eradication can also induce mucosal dysfunction with changes in the microRNA (miRNA) profile, which might drive the development of gastric carcinogenesis. […] Investigating bile acid-induced IM is important and necessary for the prevention of GC.

• #33 Biliary reflux after bariatric surgery and after gastroesophageal surgery for gastroesophageal reflux disease – Marabotto – Digestive Medicine Research

  https://dmr.amegroups.org/article/view/9258/html

  Biliary reflux refers to the ascent of duodenal fluid, biliary and pancreatic secretions into the stomach and esophagus. It is a primitive phenomenon or it can be secondary to gastric or biliary surgery. In particular, biliary reflux seems common after bariatric surgeries with, however, unknown incidence. Current data show that the prevalence of biliary reflux was higher after minigastric bypass as compared to the other bariatric surgeries. Nevertheless, biliary reflux resulted to be a relevant risk factor for the development of reflux-related complications, such as erosive esophagitis and Barrett esophagus, and its persistence over time seems to be an independent risk factor for gastric cancer. The likely mechanism of bile acids inducing esophageal symptoms is the release of intercellular mediators via damage to lipid membranes. The reflux of duodenal contents via the stomach into the esophagus is also able to induce mucosal injury and this has been shown both in animals and in humans. Conjugated bile acids enter the mucosal cells in unionized form (predominant form at low pH) through the lipophilic lipid membrane and then accumulate as intracellular ionization results in entrapment. This high concentration of bile acids causes intracellular damage by the dissolution of cell membranes and tight junctions. The pathogenetic role in the esophagus of duodenal contents consisting of bilirubin, bile acids and pancreatic enzymes have been confirmed by the development of erosive esophagitis in patients undergoing total gastrectomy or in those with achlorhydria. Moreover, esophageal exposure to both acid and DGER was shown to be present in 100% of patients with complicated Barretts esophagus, 89% of uncomplicated Barretts esophagus, 75% of erosive esophagitis and 50% of NERD by using combined 24-hour pH and Bilitec monitoring. These latter findings by Vaezi et al. confirm that there is a synergy between acid and DGER, which contributes to induce not only the presence but also the severity of esophageal mucosal lesions. Biliary reflux could be easily misdiagnosed or misinterpreted, but considering the certified involvement in the pathogenesis of precancerous lesions, its evaluation is pivotal. Moreover, other studies have documented that bile reflux is an independent risk factor for gastric cancer, thus highlighting the importance of its assessment.

• #34 Reflux Esophagitis Pathology: Definition, Epidemiology, Etiology

  https://emedicine.medscape.com/article/1610393-overview

  The presence of bile in reflux contents is increasingly being thought to contribute to reflux disease in a subset of cases, as observed in patients on proton pump inhibitor (PPI) therapy. […] Bile refluxate contains bile acids (both conjugated and unconjugated) and trypsin. Animal studies have shown that conjugated bile acids induce mucosal damage in an acidic environment and unconjugated bile acids and trypsin are responsible for mucosal damage at more neutral pH values (pH 5-8). […] At the molecular level, bile acids stimulate squamous esophageal cells to produce inflammatory mediators and cause oxidative stress, DNA damage, and increased apoptosis. […] Occasional reflux of gastric contents into the esophagus is a universal phenomenon, and the majority of people do not develop reflux disease because of intact antireflux mechanisms, which clear the refluxed contents back into the stomach before damage is done. […] Poor or abnormal LES function is the most common cause of GERD. […] The acidic nature of the refluxed gastric content is predominantly responsible for esophageal mucosal damage and the subsequent development of reflux esophagitis.

• #35 Reflux Esophagitis Pathology: Definition, Epidemiology, Etiology

  https://emedicine.medscape.com/article/1610393-overview

  The presence of bile in reflux contents is increasingly being thought to contribute to reflux disease in a subset of cases, as observed in patients on proton pump inhibitor (PPI) therapy. […] Bile refluxate contains bile acids (both conjugated and unconjugated) and trypsin. Animal studies have shown that conjugated bile acids induce mucosal damage in an acidic environment and unconjugated bile acids and trypsin are responsible for mucosal damage at more neutral pH values (pH 5-8). […] At the molecular level, bile acids stimulate squamous esophageal cells to produce inflammatory mediators and cause oxidative stress, DNA damage, and increased apoptosis. […] Occasional reflux of gastric contents into the esophagus is a universal phenomenon, and the majority of people do not develop reflux disease because of intact antireflux mechanisms, which clear the refluxed contents back into the stomach before damage is done. […] Poor or abnormal LES function is the most common cause of GERD. […] The acidic nature of the refluxed gastric content is predominantly responsible for esophageal mucosal damage and the subsequent development of reflux esophagitis.

• #36 Medical management of acid/bile reflux before, during and after endoscopic therapy for Barrett’s esophagus: a narrative review – Jaswani – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5859/html

  Persistent gastric acid exposure to the distal esophagus has been identified in the pathogenesis of BE. […] Bile reflux or duodenogastric reflux has been proposed in the etiology of BE as bile acids have been found in the refluxate of patients with BE. It has been suggested that bile acids may exert their effects on the esophageal mucosa through cytotoxic pathways and upregulation of proto-oncogene and c-myc resulting in inflammation and contributing to the inflammation-cancer cascade. […] Bile acids become non-ionized at acidic pH, enters cells and exert mucosal injury and inflammation. […] The effect of bile acid has been found to be most significant when combined with gastric acid. […] Inadequate acid suppression defined by impedance-pH monitoring is a modifiable risk factor and increases the risk of recurrence of intestinal metaplasia (IM) after EET.

• #37 Medical management of acid/bile reflux before, during and after endoscopic therapy for Barrett’s esophagus: a narrative review – Jaswani – Annals of Esophagus

  https://aoe.amegroups.org/article/view/5859/html

  Persistent gastric acid exposure to the distal esophagus has been identified in the pathogenesis of BE. […] Bile reflux or duodenogastric reflux has been proposed in the etiology of BE as bile acids have been found in the refluxate of patients with BE. It has been suggested that bile acids may exert their effects on the esophageal mucosa through cytotoxic pathways and upregulation of proto-oncogene and c-myc resulting in inflammation and contributing to the inflammation-cancer cascade. […] Bile acids become non-ionized at acidic pH, enters cells and exert mucosal injury and inflammation. […] The effect of bile acid has been found to be most significant when combined with gastric acid. […] Inadequate acid suppression defined by impedance-pH monitoring is a modifiable risk factor and increases the risk of recurrence of intestinal metaplasia (IM) after EET.

• #38 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  We found that duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] These findings not only confirm but extend previous case reports and indicate that cholecystectomy significantly increases the risk of duodenogastric bile reflux and causes more severe symptoms of functional dyspepsia, necessitating a need for stronger analgesia in many patients. […] Irrespective of the predisposing factors, prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance. […] The degree and duration of bile exposure that is needed to develop gastropathy is not fully understood, but once developed it manifests as gastric mucosal edema and hyperemia along with symptoms of functional dyspepsia.

• #39 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/journal/view.html?spage=400&volume=27&number=3

  Bile reflux gastropathy is associated with functional dyspepsia and causes more severe symptoms. […] Cholecystectomy predisposes to BG and abnormal pain, and could contribute to the pathogenesis of functional dyspepsia. […] The pathoetiology of functional dyspepsia remains unclear; one mechanism could be chemical gastropathy from chronic bile reflux. […] Gastric luminal irritants include the reflux of duodenal contents into the stomach such as bile salts, alkaline pancreatic, and duodenal secretions, lysolecithin, or ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). […] Cholecystectomy may serve as a risk factor for bile reflux into the stomach. […] Prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance.

• #40 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/journal/view.html?spage=400&volume=27&number=3

  Bile reflux gastropathy is associated with functional dyspepsia and causes more severe symptoms. […] Cholecystectomy predisposes to BG and abnormal pain, and could contribute to the pathogenesis of functional dyspepsia. […] The pathoetiology of functional dyspepsia remains unclear; one mechanism could be chemical gastropathy from chronic bile reflux. […] Gastric luminal irritants include the reflux of duodenal contents into the stomach such as bile salts, alkaline pancreatic, and duodenal secretions, lysolecithin, or ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). […] Cholecystectomy may serve as a risk factor for bile reflux into the stomach. […] Prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance.

• #41 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/journal/view.html?spage=400&volume=27&number=3

  Bile reflux gastropathy is associated with functional dyspepsia and causes more severe symptoms. […] Cholecystectomy predisposes to BG and abnormal pain, and could contribute to the pathogenesis of functional dyspepsia. […] The pathoetiology of functional dyspepsia remains unclear; one mechanism could be chemical gastropathy from chronic bile reflux. […] Gastric luminal irritants include the reflux of duodenal contents into the stomach such as bile salts, alkaline pancreatic, and duodenal secretions, lysolecithin, or ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). […] Cholecystectomy may serve as a risk factor for bile reflux into the stomach. […] Prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance.

• #42 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  We found that duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] These findings not only confirm but extend previous case reports and indicate that cholecystectomy significantly increases the risk of duodenogastric bile reflux and causes more severe symptoms of functional dyspepsia, necessitating a need for stronger analgesia in many patients. […] Irrespective of the predisposing factors, prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance. […] The degree and duration of bile exposure that is needed to develop gastropathy is not fully understood, but once developed it manifests as gastric mucosal edema and hyperemia along with symptoms of functional dyspepsia.

• #43 Biliary reflux after bariatric surgery and after gastroesophageal surgery for gastroesophageal reflux disease – Marabotto – Digestive Medicine Research

  https://dmr.amegroups.org/article/view/9258/html

  Biliary reflux refers to the ascent of duodenal fluid, biliary and pancreatic secretions into the stomach and esophagus. It is a primitive phenomenon or it can be secondary to gastric or biliary surgery. In particular, biliary reflux seems common after bariatric surgeries with, however, unknown incidence. Current data show that the prevalence of biliary reflux was higher after minigastric bypass as compared to the other bariatric surgeries. Nevertheless, biliary reflux resulted to be a relevant risk factor for the development of reflux-related complications, such as erosive esophagitis and Barrett esophagus, and its persistence over time seems to be an independent risk factor for gastric cancer. The likely mechanism of bile acids inducing esophageal symptoms is the release of intercellular mediators via damage to lipid membranes. The reflux of duodenal contents via the stomach into the esophagus is also able to induce mucosal injury and this has been shown both in animals and in humans. Conjugated bile acids enter the mucosal cells in unionized form (predominant form at low pH) through the lipophilic lipid membrane and then accumulate as intracellular ionization results in entrapment. This high concentration of bile acids causes intracellular damage by the dissolution of cell membranes and tight junctions. The pathogenetic role in the esophagus of duodenal contents consisting of bilirubin, bile acids and pancreatic enzymes have been confirmed by the development of erosive esophagitis in patients undergoing total gastrectomy or in those with achlorhydria. Moreover, esophageal exposure to both acid and DGER was shown to be present in 100% of patients with complicated Barretts esophagus, 89% of uncomplicated Barretts esophagus, 75% of erosive esophagitis and 50% of NERD by using combined 24-hour pH and Bilitec monitoring. These latter findings by Vaezi et al. confirm that there is a synergy between acid and DGER, which contributes to induce not only the presence but also the severity of esophageal mucosal lesions. Biliary reflux could be easily misdiagnosed or misinterpreted, but considering the certified involvement in the pathogenesis of precancerous lesions, its evaluation is pivotal. Moreover, other studies have documented that bile reflux is an independent risk factor for gastric cancer, thus highlighting the importance of its assessment.

• #44 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36134174/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] Besides, researches have established that BRG is closely associated with the development of precancerous lesions and gastric cancer. […] Inflammation (hyperemia, edema, erosion) stimulation of bile acids, lysolecithin, and so on. […] In this review, we briefly evaluate this disorder based on the best available evidence, offering an overview of its complicated pathogenesis, diverse relevant factors, potential carcinomatous risk, modern diagnostic investigations, and effective therapeutic plans.

• #45 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #46

  https://link.springer.com/article/10.1007/s00534-008-0010-5

  Refluxed bile may activate pancreatic enzymes, particularly phospholipase A2, which may result in cause acute pancreatitis. […] Given Opies common channel theory, in which obstruction of outflow below the common bile duct and the pancreatic duct would permit bile flow into the pancreas, acute biliary pancreatitis would seem to occur more readily in HCPBD patients with a relatively long common channel. […] The rate of pancreatitis was different in patients with PBM (4%) and HCPBD (28%). […] Biliopancreatic reflux can occur frequently in PBM or HCPBD patients; it can also occur in some individuals without these conditions. The true prevalence, degree, and precise pathophysiology of biliopancreatic reflux remain unclear. Nevertheless, biliopancreatic reflux is thought to be related to the occurrence of acute pancreatitis.

• #47 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  Bile reflux gastropathy is associated with functional dyspepsia and causes more severe symptoms. Cholecystectomy predisposes to BG and abnormal pain, and could contribute to the pathogenesis of functional dyspepsia. […] The pathoetiology of functional dyspepsia remains unclear; one mechanism could be chemical gastropathy from chronic bile reflux. […] Gastric luminal irritants include the reflux of duodenal contents into the stomach such as bile salts, alkaline pancreatic, and duodenal secretions, lysolecithin, or ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). All of these agents can cause chemical injury to the mucosa leading to a reactive or chemical gastropathy. […] Cholecystectomy may serve as a risk factor for bile reflux into the stomach. […] The aim of our study is to evaluate whether bile reflux into the stomach could contribute to the development of functional dyspepsia symptoms, by assessing the demographic, clinical, endoscopic, and gastrointestinal motility characteristics in a cohort of patients with bile gastropathy (BG) and comparing this with patients categorized as non-bile gastropathy (NBG) or no gastropathy (NG).

• #48 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #49 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36134174/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] Besides, researches have established that BRG is closely associated with the development of precancerous lesions and gastric cancer. […] Inflammation (hyperemia, edema, erosion) stimulation of bile acids, lysolecithin, and so on. […] In this review, we briefly evaluate this disorder based on the best available evidence, offering an overview of its complicated pathogenesis, diverse relevant factors, potential carcinomatous risk, modern diagnostic investigations, and effective therapeutic plans.

• #50 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #51 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #52 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Inflammation is primarily aroused by the stimulation of reflux contents. Among them, bile acids and lysolecithin are the major components that destroy the barrier on the surface of gastric mucosa by dissolving phospholipids and cholesterol, which motivates hydrogen ions in gastric juice to diffuse into gastric mucosa for the increased permeability of gastric epithelial cells. […] More and more studies have established that bile reflux gastritis is closely associated with the development of precancerous lesions and gastric cancer (GC) and may be an independent risk factor for GC. […] The mechanism of GC induced by bile reflux is still unclear. Microscopically, it was reported that exposure to a high concentration of bile acids increased the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could cause DNA damage and mutations of genes like p53, participating in human carcinogenesis.

• #53 Does Bile Reflux Increase Following Cholecystectomy? – Houston Heartburn and Reflux Center

  https://houstonheartburn.com/does-bile-reflux-increase-following-cholecystectomy/

  “Gastroesophageal Mucosal Injury after Cholecystectomy: An Indication for Surveillance?” is a new study published by T. Walsh et al in the current issue of JACS (Journal of the American College of Surgeons). The authors evaluate the incidence of stomach bile pooling detected by endoscopy in patients before and after cholecystectomy. They further measure the bile reflux index, cellular proliferation marker Ki67 and tumor-suppressor gene p53 in biopsies taken from the gastro-esophageal junction and gastric antrum. The analysis show that cholecystectomy increases the incidence of bile reflux and bile induced damage of gastric and esophageal mucosa. Chronic bile induced esophagitis and gastritis increase the incidence of gastric and esophageal cancer. The role of bile reflux in the pathogenesis of Barrett’s esophagus is well established and 10% of patients with Barrett’s esophagus develop esophageal adenocarcinoma. […] This study shows that cholecystectomy increases the risk of bile reflux and esophago-gastric mucosa injury. I suspect the risk of bile reflux and mucosal injury is highest in GERD patients who undergo an unindicated cholecystectomy.

• #54 Bile reflux and hypopharyngeal cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2021.8195

  The above observations strongly support that controlling the pH during reflux episodes may have a protective effect by reducing the risk of bile-induced hypopharyngeal cancer. […] The role of NF-B in acidic bile reflux-related laryngopharyngeal carcinogenesis was first demonstrated in the last decade through in vitro and in vivo experimental models. […] A study by our group from 2017 documented the key role of NF-B in mediating acidic bile-induced oncogenic molecular events in human hypopharyngeal cells (HHCs). […] Preclinical studies from our group documented that acidic bile is able to induce activation of NF-B and significant overexpression of several cancer-related genes. […] These results revealed that the upregulation of RELA, BCL2, STAT3, EGFR, WNT5A, TNF-, IL6 and PTGS2 is directly promoted by acidic bile through NF-B, shortly after its exposure, and strongly suggested that it may be clinically feasible to topically apply NF-B inhibitors, without any precise synchronization with acidic bile exposure, to prevent acidic bile-induced oncogenic molecular changes.

• #55 Bile reflux and hypopharyngeal cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2021.8195

  The above observations strongly support that controlling the pH during reflux episodes may have a protective effect by reducing the risk of bile-induced hypopharyngeal cancer. […] The role of NF-B in acidic bile reflux-related laryngopharyngeal carcinogenesis was first demonstrated in the last decade through in vitro and in vivo experimental models. […] A study by our group from 2017 documented the key role of NF-B in mediating acidic bile-induced oncogenic molecular events in human hypopharyngeal cells (HHCs). […] Preclinical studies from our group documented that acidic bile is able to induce activation of NF-B and significant overexpression of several cancer-related genes. […] These results revealed that the upregulation of RELA, BCL2, STAT3, EGFR, WNT5A, TNF-, IL6 and PTGS2 is directly promoted by acidic bile through NF-B, shortly after its exposure, and strongly suggested that it may be clinically feasible to topically apply NF-B inhibitors, without any precise synchronization with acidic bile exposure, to prevent acidic bile-induced oncogenic molecular changes.

• #56 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  When bile reflux occurs, secondary bile acids and free bile acids are regurgitated into the stomach. […] Bile acids inhibit the activity of NO enzyme and the sodium hydrogen exchange of cells, leading to intracellular DNA damage, apoptosis, and mutation. […] Bile reflux can stimulate gastrin secretion from G cells, which promotes gastric acid secretion and inhibits pyloric sphincter contraction, further promoting bile reflux and forming a vicious circle. […] Recent studies have shown that acidic bile acids in gastric juice after successful Hp eradication can also induce mucosal dysfunction with changes in the microRNA (miRNA) profile, which might drive the development of gastric carcinogenesis. […] Investigating bile acid-induced IM is important and necessary for the prevention of GC.

• #57 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  Another study demonstrated that the incidence of GC was at a high rate of 41% in a rat model of bile reflux. […] Recent studies have shown that IM biomarkers, microRNAs (miRNAs), exosomes, and epigenetic modifications are associated with gastric IM. […] Studies have shown that bile acids induced the expression of miR-21, which could inhibit the expression of SOX2 by directly binding its 3-UTR and abrogate its suppression on the transcriptional activity of CDX2, thus leading to IM. […] Bile acids promote gastric IM through HNF4a/HDCA6/CDX2 pathway in vivo and in vitro. […] Therefore, more studies are needed to further investigate whether the mechanism of bile reflux can be targeted to reverse IM.

• #58 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  A peptic ulcer can block the pyloric valve so that it doesn’t open or close properly. […] People who have had their gallbladders removed have significantly more bile reflux than do people who haven’t had this surgery. […] Bile reflux gastritis has been linked to stomach cancer. […] The combination of bile reflux and acid reflux also increases the risk of the following complications: […] Bile is often suspected of contributing to GERD when people respond incompletely or not at all to powerful acid-suppressant medications. […] Animal studies have also linked bile reflux to Barrett’s esophagus. […] In animal studies, bile reflux alone has been shown to cause cancer of the esophagus.

• #59 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. […] However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. […] The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. […] Increasing evidence has demonstrated that bile reflux is thought to be associated with atrophic gastritis, IM, dysplasia, and even carcinogenesis. […] The mechanism of bile acid-induced gastric IM in the stomach is not clear and needs further research. […] Bile reflux, also known as duodenogastric reflux, refers to the backflow of duodenal contents, including bile, pancreatic juice, and duodenal juice, into the stomach.

• #60 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  Another study demonstrated that the incidence of GC was at a high rate of 41% in a rat model of bile reflux. […] Recent studies have shown that IM biomarkers, microRNAs (miRNAs), exosomes, and epigenetic modifications are associated with gastric IM. […] Studies have shown that bile acids induced the expression of miR-21, which could inhibit the expression of SOX2 by directly binding its 3-UTR and abrogate its suppression on the transcriptional activity of CDX2, thus leading to IM. […] Bile acids promote gastric IM through HNF4a/HDCA6/CDX2 pathway in vivo and in vitro. […] Therefore, more studies are needed to further investigate whether the mechanism of bile reflux can be targeted to reverse IM.

• #61 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  Another study demonstrated that the incidence of GC was at a high rate of 41% in a rat model of bile reflux. […] Recent studies have shown that IM biomarkers, microRNAs (miRNAs), exosomes, and epigenetic modifications are associated with gastric IM. […] Studies have shown that bile acids induced the expression of miR-21, which could inhibit the expression of SOX2 by directly binding its 3-UTR and abrogate its suppression on the transcriptional activity of CDX2, thus leading to IM. […] Bile acids promote gastric IM through HNF4a/HDCA6/CDX2 pathway in vivo and in vitro. […] Therefore, more studies are needed to further investigate whether the mechanism of bile reflux can be targeted to reverse IM.

• #62 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  Another study demonstrated that the incidence of GC was at a high rate of 41% in a rat model of bile reflux. […] Recent studies have shown that IM biomarkers, microRNAs (miRNAs), exosomes, and epigenetic modifications are associated with gastric IM. […] Studies have shown that bile acids induced the expression of miR-21, which could inhibit the expression of SOX2 by directly binding its 3-UTR and abrogate its suppression on the transcriptional activity of CDX2, thus leading to IM. […] Bile acids promote gastric IM through HNF4a/HDCA6/CDX2 pathway in vivo and in vitro. […] Therefore, more studies are needed to further investigate whether the mechanism of bile reflux can be targeted to reverse IM.

• #63 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. […] However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. […] The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. […] Increasing evidence has demonstrated that bile reflux is thought to be associated with atrophic gastritis, IM, dysplasia, and even carcinogenesis. […] The mechanism of bile acid-induced gastric IM in the stomach is not clear and needs further research. […] Bile reflux, also known as duodenogastric reflux, refers to the backflow of duodenal contents, including bile, pancreatic juice, and duodenal juice, into the stomach.

• #64 Management of Bile Reflux – Gastroenterology & Hepatology

  https://www.gastroenterologyandhepatology.net/archives/march-2013/management-of-bile-reflux/

  Bile reflux is very infrequent in healthy individuals. This condition is more severe in patients with gastroesophageal reflux disease, particularly those with severe esophagitis and/or Barrett esophagus. […] It has been shown that patients with more bile reflux have more severe esophageal mucosal damage, so there is a clear correlation between the amount of bile reflux and the severity of distal esophageal inflammation. In fact, patients with the most severe degree of gastroesophageal inflammation, Barrett esophagus, are those with the largest amount of bile reflux. Thus, the importance of bile reflux has to do primarily with the severity of the damage of the esophageal mucosa, the development of Barrett mucosa, and, potentially, the risk of cancer. It is known that the more bile reflux a patient has, the higher the risk of Barrett esophagus development; both in vivo and in vitro studies have shown a link between bile that is in contact with esophageal mucosa and changes in the mucosa that are compatible with Barrett esophagus.

• #65 Biliary reflux after bariatric surgery and after gastroesophageal surgery for gastroesophageal reflux disease – Marabotto – Digestive Medicine Research

  https://dmr.amegroups.org/article/view/9258/html

  Biliary reflux refers to the ascent of duodenal fluid, biliary and pancreatic secretions into the stomach and esophagus. It is a primitive phenomenon or it can be secondary to gastric or biliary surgery. In particular, biliary reflux seems common after bariatric surgeries with, however, unknown incidence. Current data show that the prevalence of biliary reflux was higher after minigastric bypass as compared to the other bariatric surgeries. Nevertheless, biliary reflux resulted to be a relevant risk factor for the development of reflux-related complications, such as erosive esophagitis and Barrett esophagus, and its persistence over time seems to be an independent risk factor for gastric cancer. The likely mechanism of bile acids inducing esophageal symptoms is the release of intercellular mediators via damage to lipid membranes. The reflux of duodenal contents via the stomach into the esophagus is also able to induce mucosal injury and this has been shown both in animals and in humans. Conjugated bile acids enter the mucosal cells in unionized form (predominant form at low pH) through the lipophilic lipid membrane and then accumulate as intracellular ionization results in entrapment. This high concentration of bile acids causes intracellular damage by the dissolution of cell membranes and tight junctions. The pathogenetic role in the esophagus of duodenal contents consisting of bilirubin, bile acids and pancreatic enzymes have been confirmed by the development of erosive esophagitis in patients undergoing total gastrectomy or in those with achlorhydria. Moreover, esophageal exposure to both acid and DGER was shown to be present in 100% of patients with complicated Barretts esophagus, 89% of uncomplicated Barretts esophagus, 75% of erosive esophagitis and 50% of NERD by using combined 24-hour pH and Bilitec monitoring. These latter findings by Vaezi et al. confirm that there is a synergy between acid and DGER, which contributes to induce not only the presence but also the severity of esophageal mucosal lesions. Biliary reflux could be easily misdiagnosed or misinterpreted, but considering the certified involvement in the pathogenesis of precancerous lesions, its evaluation is pivotal. Moreover, other studies have documented that bile reflux is an independent risk factor for gastric cancer, thus highlighting the importance of its assessment.

• #66 Management of Bile Reflux – Gastroenterology & Hepatology

  https://www.gastroenterologyandhepatology.net/archives/march-2013/management-of-bile-reflux/

  Bile reflux is very infrequent in healthy individuals. This condition is more severe in patients with gastroesophageal reflux disease, particularly those with severe esophagitis and/or Barrett esophagus. […] It has been shown that patients with more bile reflux have more severe esophageal mucosal damage, so there is a clear correlation between the amount of bile reflux and the severity of distal esophageal inflammation. In fact, patients with the most severe degree of gastroesophageal inflammation, Barrett esophagus, are those with the largest amount of bile reflux. Thus, the importance of bile reflux has to do primarily with the severity of the damage of the esophageal mucosa, the development of Barrett mucosa, and, potentially, the risk of cancer. It is known that the more bile reflux a patient has, the higher the risk of Barrett esophagus development; both in vivo and in vitro studies have shown a link between bile that is in contact with esophageal mucosa and changes in the mucosa that are compatible with Barrett esophagus.

• #67 Management of Bile Reflux – Gastroenterology & Hepatology

  https://www.gastroenterologyandhepatology.net/archives/march-2013/management-of-bile-reflux/

  Bile reflux is very infrequent in healthy individuals. This condition is more severe in patients with gastroesophageal reflux disease, particularly those with severe esophagitis and/or Barrett esophagus. […] It has been shown that patients with more bile reflux have more severe esophageal mucosal damage, so there is a clear correlation between the amount of bile reflux and the severity of distal esophageal inflammation. In fact, patients with the most severe degree of gastroesophageal inflammation, Barrett esophagus, are those with the largest amount of bile reflux. Thus, the importance of bile reflux has to do primarily with the severity of the damage of the esophageal mucosa, the development of Barrett mucosa, and, potentially, the risk of cancer. It is known that the more bile reflux a patient has, the higher the risk of Barrett esophagus development; both in vivo and in vitro studies have shown a link between bile that is in contact with esophageal mucosa and changes in the mucosa that are compatible with Barrett esophagus.

• #68 Management of Bile Reflux – Gastroenterology & Hepatology

  https://www.gastroenterologyandhepatology.net/archives/march-2013/management-of-bile-reflux/

  Bile reflux is very infrequent in healthy individuals. This condition is more severe in patients with gastroesophageal reflux disease, particularly those with severe esophagitis and/or Barrett esophagus. […] It has been shown that patients with more bile reflux have more severe esophageal mucosal damage, so there is a clear correlation between the amount of bile reflux and the severity of distal esophageal inflammation. In fact, patients with the most severe degree of gastroesophageal inflammation, Barrett esophagus, are those with the largest amount of bile reflux. Thus, the importance of bile reflux has to do primarily with the severity of the damage of the esophageal mucosa, the development of Barrett mucosa, and, potentially, the risk of cancer. It is known that the more bile reflux a patient has, the higher the risk of Barrett esophagus development; both in vivo and in vitro studies have shown a link between bile that is in contact with esophageal mucosa and changes in the mucosa that are compatible with Barrett esophagus.

• #69 Management of Bile Reflux – Gastroenterology & Hepatology

  https://www.gastroenterologyandhepatology.net/archives/march-2013/management-of-bile-reflux/

  Bile reflux is very infrequent in healthy individuals. This condition is more severe in patients with gastroesophageal reflux disease, particularly those with severe esophagitis and/or Barrett esophagus. […] It has been shown that patients with more bile reflux have more severe esophageal mucosal damage, so there is a clear correlation between the amount of bile reflux and the severity of distal esophageal inflammation. In fact, patients with the most severe degree of gastroesophageal inflammation, Barrett esophagus, are those with the largest amount of bile reflux. Thus, the importance of bile reflux has to do primarily with the severity of the damage of the esophageal mucosa, the development of Barrett mucosa, and, potentially, the risk of cancer. It is known that the more bile reflux a patient has, the higher the risk of Barrett esophagus development; both in vivo and in vitro studies have shown a link between bile that is in contact with esophageal mucosa and changes in the mucosa that are compatible with Barrett esophagus.

• #70 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  A peptic ulcer can block the pyloric valve so that it doesn’t open or close properly. […] People who have had their gallbladders removed have significantly more bile reflux than do people who haven’t had this surgery. […] Bile reflux gastritis has been linked to stomach cancer. […] The combination of bile reflux and acid reflux also increases the risk of the following complications: […] Bile is often suspected of contributing to GERD when people respond incompletely or not at all to powerful acid-suppressant medications. […] Animal studies have also linked bile reflux to Barrett’s esophagus. […] In animal studies, bile reflux alone has been shown to cause cancer of the esophagus.

• #71 Bile reflux and hypopharyngeal cancer (Review)

  https://www.spandidos-publications.com/10.3892/or.2021.8195

  Laryngopharyngeal reflux, a variant of gastroesophageal reflux disease, has been considered a risk factor in the development of hypopharyngeal cancer. […] Recent in vitro and in vivo studies have provided direct evidence of the role of acidic bile refluxate in hypopharyngeal carcinogenesis and documented the crucial role of NFB as a key mediator of early oncogenic molecular events in this process and also suggested a contribution of STAT3. […] Acidic bile can cause premalignant changes and invasive squamous cell cancer in the affected hypopharynx accompanied by DNA damage, elevated p53 expression and oncogenic mRNA and microRNA alterations, previously linked to head and neck cancer. […] Weakly acidic bile can also increase the risk for hypopharyngeal carcinogenesis by inducing DNA damage, exerting antiapoptotic effects and causing precancerous lesions.

• #72 Bile Reflux: Symptoms, Treatment, Causes & What It Is

  https://my.clevelandclinic.org/health/diseases/22056-bile-reflux

  Bile is produced in your liver, stored in your gallbladder and released into your small intestine when there are fats there to digest. The pyloric valve lets food out of your stomach and into your small intestine, where it mixes with bile. If the pyloric valve is too relaxed, or maybe obstructed, it doesnt close properly, and bile can flow back into your stomach. […] Chronic bile reflux can erode these protective linings, causing painful inflammation and, eventually, tissue damage (esophagitis). […] Chronic inflammation of your stomach lining (gastritis) can lead to stomach ulcers and is associated with a higher risk of stomach cancer. Inflammation of your esophagus (esophagitis) can cause ulcers, scarring and cellular changes to your lining (Barretts Esophagus), which is occasionally a precursor to esophageal cancer. These risks are also associated with chronic gastroesophageal acid reflux (GERD), but studies show that bile reflux multiplies the risk.

• #73 Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review | Cell Death Discovery

  https://www.nature.com/articles/s41420-022-00962-1

  Another study demonstrated that the incidence of GC was at a high rate of 41% in a rat model of bile reflux. […] Recent studies have shown that IM biomarkers, microRNAs (miRNAs), exosomes, and epigenetic modifications are associated with gastric IM. […] Studies have shown that bile acids induced the expression of miR-21, which could inhibit the expression of SOX2 by directly binding its 3-UTR and abrogate its suppression on the transcriptional activity of CDX2, thus leading to IM. […] Bile acids promote gastric IM through HNF4a/HDCA6/CDX2 pathway in vivo and in vitro. […] Therefore, more studies are needed to further investigate whether the mechanism of bile reflux can be targeted to reverse IM.

• #74 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #75 Biliary reflux – Wikipedia

  https://en.wikipedia.org/wiki/Biliary_reflux

  Biliary reflux, also called bile reflux, duodenogastroesophageal reflux (DGER) or duodenogastric reflux, is a condition that occurs when bile and/or other contents like bicarbonate and pancreatic enzymes flow upward (refluxes) from the duodenum into the stomach and esophagus. […] Bile is a digestive fluid made by the liver, stored in the gallbladder, and discharged into the duodenum after food is ingested to aid in the digestion of fat. Normally, the pyloric sphincter prevents bile from entering the stomach. When the pyloric sphincter is damaged or fails to work correctly, bile can enter the stomach and then be transported into the esophagus as in gastric reflux. The presence of small amounts of bile in the stomach is relatively common and usually asymptomatic, but excessive refluxed bile causes irritation and inflammation.

• #76 Bile reflux: Symptoms, causes, treatment and more

  https://www.medicalnewstoday.com/articles/bile-reflux

  Bile reflux can happen for the following reasons: as a complication of surgery, such as bariatric or gallbladder surgery; due to a structural problem with an esophageal valve, which allows the food and bile to flow back up into the esophagus; due to a problem with the function of the gastric valve called the pyloric valve, which may occur due to peptic ulcers. […] Bile reflux usually requires medications and, sometimes, surgery. If left untreated, bile reflux can irritate the GI tract and increase the risk of complications.

• #77 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  A peptic ulcer can block the pyloric valve so that it doesn’t open or close properly. […] People who have had their gallbladders removed have significantly more bile reflux than do people who haven’t had this surgery. […] Bile reflux gastritis has been linked to stomach cancer. […] The combination of bile reflux and acid reflux also increases the risk of the following complications: […] Bile is often suspected of contributing to GERD when people respond incompletely or not at all to powerful acid-suppressant medications. […] Animal studies have also linked bile reflux to Barrett’s esophagus. […] In animal studies, bile reflux alone has been shown to cause cancer of the esophagus.

• #78 Bile Reflux: Symptoms, Treatment, Causes & What It Is

  https://my.clevelandclinic.org/health/diseases/22056-bile-reflux

  Bile reflux occurs when the valves that keep bile from backwashing into your stomach and esophagus arent working properly. Bile can erode the delicate linings of your stomach and esophagus, causing inflammation and tissue damage. […] Bile reflux occurs when bile from the small intestine backwashes into the stomach, and sometimes into the esophagus. Bile refluxes from the small intestine into the stomach and esophagus. […] Normally, everything involved in the digestive process should only flow one way down. As food progresses along the digestive tract, valves at the end of each organ open just enough to let food and digestive juices through into the next, without letting anything flow back the other way. But if these valves (sphincters) arent functioning right, reflux can happen, and digestive juices like bile can flow back into organs where they dont belong.

• #79 Bile Reflux: Clinical Considerations – Gastroenterology Advisor

  https://www.gastroenterologyadvisor.com/features/tips-for-distinguishing-and-treating-biliary-reflux/

  Bile reflux occurs when the bile secreted into the duodenum moves retrograde into the stomach and potentially into the esophagus. […] In certain patients with bile reflux, it has been postulated that a weak or widely patent pylorus could predispose patients to this condition. […] Bile reflux may also be more common in patients with motility disorders, especially in those whose gastric or duodenal motility is reduced, including certain patients with type 2 diabetes mellitus or those taking chronic opioid medications. […] Patients who have undergone gastric surgeries where the pylorus is bypassed or disrupted may be predisposed to developing bile reflux as well. […] Bile reflux is typically alkaline in nature, compared with the acidic environment found in the stomach. […] Despite this difference in pH, patients can experience similar symptoms, making bile reflux and GERD difficult to distinguish.

• #80 Bile Reflux: Symptoms, Treatment, Causes & What It Is

  https://my.clevelandclinic.org/health/diseases/22056-bile-reflux

  Bile reflux occurs when the valves that keep bile from backwashing into your stomach and esophagus arent working properly. Bile can erode the delicate linings of your stomach and esophagus, causing inflammation and tissue damage. […] Bile reflux occurs when bile from the small intestine backwashes into the stomach, and sometimes into the esophagus. Bile refluxes from the small intestine into the stomach and esophagus. […] Normally, everything involved in the digestive process should only flow one way down. As food progresses along the digestive tract, valves at the end of each organ open just enough to let food and digestive juices through into the next, without letting anything flow back the other way. But if these valves (sphincters) arent functioning right, reflux can happen, and digestive juices like bile can flow back into organs where they dont belong.

• #81 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  Bile reflux occurs when bile a digestive liquid produced in your liver backs up (refluxes) into your stomach and, in some cases, into the tube that connects your mouth and stomach (esophagus). […] Unlike gastric acid reflux, bile reflux can’t be completely controlled by changes in diet or lifestyle. Treatment involves medications or, in severe cases, surgery. […] In cases of bile reflux, the valve doesn’t close properly, and bile washes back into the stomach. This can lead to inflammation of the stomach lining (bile reflux gastritis). […] Bile and stomach acid can reflux into the esophagus when another muscular valve, the lower esophageal sphincter, doesn’t work properly. […] Bile reflux may be caused by: […] Stomach surgery, including total or partial removal of the stomach and gastric bypass surgery for weight loss, is responsible for most bile reflux.

• #82 Pathophysiology of gastroesophageal reflux disease – UpToDate

  https://www.uptodate.com/contents/pathophysiology-of-gastroesophageal-reflux-disease

  The development of GERD reflects an imbalance between injurious or symptom-eliciting factors (reflux events, acidity of refluxate, esophageal sensitivity) and defensive factors (esophageal acid clearance, mucosal integrity) (algorithm 1) [2,3]. […] Esophagitis results from cytokine-triggered inflammation rather than a direct chemical effect of prolonged exposure to acid, pepsin, and bile on the esophageal epithelium, the „burn” hypothesis [5-7]. […] The antireflux barrier—GERD exists as a spectrum that includes reflux esophagitis, nonerosive reflux disease, extraesophageal GERD, reflux hypersensitivity, and Barrett’s esophagus [4].

• #83 Bile or Acid Reflux Post One-Anastomosis Gastric Bypass: What Must We Do? Still an Unsolved Enigma

  https://www.mdpi.com/2077-0383/11/12/3346

  The main predisposing factor in the development of GERD is the congenital or acquired insufficiency of the lower esophageal sphincter. In case of lower esophageal sphincter insufficiency, bile backflows in the esophagus and promotes GERD symptoms. However, the hypothesis of bile reflux in all cases of GERD post OAGB cannot explain the effectiveness of proton pump inhibitors (PPI) in some patients. […] The main hypothesis for the development of acid reflux is related to the excess fundal tissue of the gastric pouch responsible for acid secretion by parietal cells. This is probably caused by the formation of an inadequate “large” gastric pouch. Acid secretions in combination with insufficient LES could promote food stasis and indigestion, thus favoring GERD.

• #84 Bile Reflux: Symptoms, Causes, and Treatment

  https://www.verywellhealth.com/bile-reflux-7197821

  Bile reflux is a condition in which the bile backs up into the stomach and/or the esophagus. […] The underlying cause may be: A structural problem with the valve in the stomach (pyloric valve), which can be due to peptic ulcers. […] If an ulcer affects the pyloric valve, it could prevent the valve from opening and closing properly. This could allow bile to back up into the stomach. […] The lower esophageal sphincter is a valve at the bottom of the esophagus. It opens up to allow food to pass from the esophagus into the stomach. […] However, if the lower esophageal sphincter is weak or too relaxed, food and bile can come back up into the esophagus. […] Having bile acids flow into the stomach or esophagus can cause damage and inflammation. If this continues for a long time, it can increase cancer risk.

• #85 Laryngopharyngeal reflux disease: Updated examination of mechanisms, pathophysiology, treatment, and association with gastroesophageal reflux disease

  https://www.wjgnet.com/1007-9327/full/v30/i16/2209.htm

  It is widely believed that the pathogenesis of LPRD includes reflux theory, reflex theory, behavioral changes and psychological factors. […] The antireflux mechanism prevents gastric contents from regurgitating into the pharynx and directly damaging the pharyngeal mucosal tissue. […] However, under pathogenic conditions, the antireflux mechanisms can be damaged individually or simultaneously, causing the gastric contents to regurgitate to the laryngopharyngeal mucosa. […] Studies have shown that the esophageal mucosa can resist 50 potential episodes of reflux per day without causing tissue damage. […] However, the laryngopharyngeal mucosa can be damaged by four reflux episodes per day. […] This indicates that the laryngopharyngeal mucosa is more fragile and more sensitive to stimulation.

• #86 Bile Reflux: Symptoms, Causes, and Treatment

  https://www.verywellhealth.com/bile-reflux-7197821

  Bile reflux is a condition in which the bile backs up into the stomach and/or the esophagus. […] The underlying cause may be: A structural problem with the valve in the stomach (pyloric valve), which can be due to peptic ulcers. […] If an ulcer affects the pyloric valve, it could prevent the valve from opening and closing properly. This could allow bile to back up into the stomach. […] The lower esophageal sphincter is a valve at the bottom of the esophagus. It opens up to allow food to pass from the esophagus into the stomach. […] However, if the lower esophageal sphincter is weak or too relaxed, food and bile can come back up into the esophagus. […] Having bile acids flow into the stomach or esophagus can cause damage and inflammation. If this continues for a long time, it can increase cancer risk.

• #87 Biliary reflux gastritis: features of pathogenesis, diagnostics and treatment | Sheptulin | Clinical Medicine (Russian Journal)

  https://www.clinmedjournal.com/jour/article/view/597?locale=en_US

  The article discusses the controversial terminology of biliary reflux gastritis and the factors predisposing to its occurrence. Pathogenesis of this disease includes 2 main components: disorders of motility of the stomach and duodenum, leading to duodeno-gastric reflux, and direct damaging effect of hydrophobic bile acids and lysolecithin on the protective barrier of the stomach mucosa. […] Given the insufficient study and controversial coverage of many aspects of biliary reflux gastritis, this problem requires further research.

• #88 Bile Reflux: Clinical Considerations – Gastroenterology Advisor

  https://www.gastroenterologyadvisor.com/features/tips-for-distinguishing-and-treating-biliary-reflux/

  Therefore, patients with evidence of bile reflux should be considered for more aggressive therapy, in the hopes of potentially preventing negative sequelae such as BE. […] It is important to note that this study found that a history of CCY was associated with bile reflux, which is most likely secondary to the unregulated and more pronounced delivery of bile into the duodenum. […] Increased levels of bile could reduce duodenal motility, making patients more prone to develop bile reflux. […] The authors concluded that duodeno-gastric bile reflux was present in at least 1/3 of patients with functional dyspepsia.

• #89

  https://link.springer.com/article/10.1007/BF02212691

  To establish the pathogenic role of duodenogastric reflux in dyspeptic symptoms we have compared the clinical features, gastrointestinal motility, and rates of duodenogastric bile reflux in 12 cholecistectomized dyspeptic patients, 12 dyspeptic patients with intact gallbladder, and 12 healthy controls. […] Fasting gastric bile acid concentrations were higher in cholecystectomized patients (P0.05) and antral postcibal motility lower (P0.05) than in the other groups. […] We concluded that patients with functional dyspepsia and a prior cholecystectomy have clinical features similar to those with gallbladders, but some physiological features are dissimilar: antral motility is decreased and duodenogastric bile reflux is increased.

• #90

  https://link.springer.com/article/10.1007/BF02212691

  To establish the pathogenic role of duodenogastric reflux in dyspeptic symptoms we have compared the clinical features, gastrointestinal motility, and rates of duodenogastric bile reflux in 12 cholecistectomized dyspeptic patients, 12 dyspeptic patients with intact gallbladder, and 12 healthy controls. […] Fasting gastric bile acid concentrations were higher in cholecystectomized patients (P0.05) and antral postcibal motility lower (P0.05) than in the other groups. […] We concluded that patients with functional dyspepsia and a prior cholecystectomy have clinical features similar to those with gallbladders, but some physiological features are dissimilar: antral motility is decreased and duodenogastric bile reflux is increased.

• #91 Bile Reflux Gastritis: Insights into Pathogenesis, Relevant Factors, Carcinomatous Risk, Diagnosis, and Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9484982/

  Bile reflux gastritis (BRG), a kind of gastrointestinal disorder in clinical practice, is characterized by regurgitation and inflammation. […] Primarily, making the pathogenesis of BRG clear contributes to a correct and general understanding of this disease for physicians. […] The occurrence of bile reflux gastritis includes two parts. One is reflux, the other is inflammation. Reflux takes place pathologically mainly due to gastroduodenal dysmotility, disorder of gastroduodenal hormones, or surgical operations. The prerequisite and foundation for it are reverse contractile activities of the duodenum and opening of the pyloric canal. Gastrointestinal hormones like gastrin, cholecystokinin, and secretin play an important role in reflux by influencing the secretion of gastric acids and regulating motility of the stomach.

• #92

  https://link.springer.com/article/10.1007/BF02212691

  To establish the pathogenic role of duodenogastric reflux in dyspeptic symptoms we have compared the clinical features, gastrointestinal motility, and rates of duodenogastric bile reflux in 12 cholecistectomized dyspeptic patients, 12 dyspeptic patients with intact gallbladder, and 12 healthy controls. […] Fasting gastric bile acid concentrations were higher in cholecystectomized patients (P0.05) and antral postcibal motility lower (P0.05) than in the other groups. […] We concluded that patients with functional dyspepsia and a prior cholecystectomy have clinical features similar to those with gallbladders, but some physiological features are dissimilar: antral motility is decreased and duodenogastric bile reflux is increased.

• #93 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  Bile reflux gastropathy is associated with functional dyspepsia and causes more severe symptoms. Cholecystectomy predisposes to BG and abnormal pain, and could contribute to the pathogenesis of functional dyspepsia. […] The pathoetiology of functional dyspepsia remains unclear; one mechanism could be chemical gastropathy from chronic bile reflux. […] Gastric luminal irritants include the reflux of duodenal contents into the stomach such as bile salts, alkaline pancreatic, and duodenal secretions, lysolecithin, or ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). All of these agents can cause chemical injury to the mucosa leading to a reactive or chemical gastropathy. […] Cholecystectomy may serve as a risk factor for bile reflux into the stomach. […] The aim of our study is to evaluate whether bile reflux into the stomach could contribute to the development of functional dyspepsia symptoms, by assessing the demographic, clinical, endoscopic, and gastrointestinal motility characteristics in a cohort of patients with bile gastropathy (BG) and comparing this with patients categorized as non-bile gastropathy (NBG) or no gastropathy (NG).

• #94 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  We found that duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] These findings not only confirm but extend previous case reports and indicate that cholecystectomy significantly increases the risk of duodenogastric bile reflux and causes more severe symptoms of functional dyspepsia, necessitating a need for stronger analgesia in many patients. […] Irrespective of the predisposing factors, prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance. […] The degree and duration of bile exposure that is needed to develop gastropathy is not fully understood, but once developed it manifests as gastric mucosal edema and hyperemia along with symptoms of functional dyspepsia.

• #95 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/journal/view.html?spage=400&volume=27&number=3

  The findings of erythematous mucosa on endoscopy together with chemical gastropathy on biopsy is not uncommon, and has been reported in 15.0% of routine screening endoscopy procedures. […] Duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] Cholecystectomy was a significant predisposing risk factor for the development of bile reflux, and was associated with more severe gastrointestinal symptoms, and use of narcotic pain medications. […] The presence of bile gastritis during an upper endoscopy together with chemical gastropathy identified by histology is essential for a diagnosis.

• #96 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  Bile reflux gastropathy is associated with functional dyspepsia and causes more severe symptoms. Cholecystectomy predisposes to BG and abnormal pain, and could contribute to the pathogenesis of functional dyspepsia. […] The pathoetiology of functional dyspepsia remains unclear; one mechanism could be chemical gastropathy from chronic bile reflux. […] Gastric luminal irritants include the reflux of duodenal contents into the stomach such as bile salts, alkaline pancreatic, and duodenal secretions, lysolecithin, or ingestion of non-steroidal anti-inflammatory drugs (NSAIDs). All of these agents can cause chemical injury to the mucosa leading to a reactive or chemical gastropathy. […] Cholecystectomy may serve as a risk factor for bile reflux into the stomach. […] The aim of our study is to evaluate whether bile reflux into the stomach could contribute to the development of functional dyspepsia symptoms, by assessing the demographic, clinical, endoscopic, and gastrointestinal motility characteristics in a cohort of patients with bile gastropathy (BG) and comparing this with patients categorized as non-bile gastropathy (NBG) or no gastropathy (NG).

• #97 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  We found that duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] These findings not only confirm but extend previous case reports and indicate that cholecystectomy significantly increases the risk of duodenogastric bile reflux and causes more severe symptoms of functional dyspepsia, necessitating a need for stronger analgesia in many patients. […] Irrespective of the predisposing factors, prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance. […] The degree and duration of bile exposure that is needed to develop gastropathy is not fully understood, but once developed it manifests as gastric mucosal edema and hyperemia along with symptoms of functional dyspepsia.

• #98 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  We found that duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] These findings not only confirm but extend previous case reports and indicate that cholecystectomy significantly increases the risk of duodenogastric bile reflux and causes more severe symptoms of functional dyspepsia, necessitating a need for stronger analgesia in many patients. […] Irrespective of the predisposing factors, prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance. […] The degree and duration of bile exposure that is needed to develop gastropathy is not fully understood, but once developed it manifests as gastric mucosal edema and hyperemia along with symptoms of functional dyspepsia.

• #99 Management of Bile Reflux – Gastroenterology & Hepatology

  https://www.gastroenterologyandhepatology.net/archives/march-2013/management-of-bile-reflux/

  The third line of research involves the role of bile in the pathogenesis of nonerosive reflux disease and symptoms. It is known that patients who have persistent symptoms such as heartburn or regurgitation may have refluxate that contains bile acid despite receiving proton pump inhibitor therapy (because proton pump inhibitors do not reduce the presence of bile acid). Bile acids might have an impact on the esophageal mucosa of patients with nonerosive reflux disease and might be related to the persistence of symptoms in these patients.

• #100

  https://link.springer.com/article/10.1007/BF02212691

  To establish the pathogenic role of duodenogastric reflux in dyspeptic symptoms we have compared the clinical features, gastrointestinal motility, and rates of duodenogastric bile reflux in 12 cholecistectomized dyspeptic patients, 12 dyspeptic patients with intact gallbladder, and 12 healthy controls. […] Fasting gastric bile acid concentrations were higher in cholecystectomized patients (P0.05) and antral postcibal motility lower (P0.05) than in the other groups. […] We concluded that patients with functional dyspepsia and a prior cholecystectomy have clinical features similar to those with gallbladders, but some physiological features are dissimilar: antral motility is decreased and duodenogastric bile reflux is increased.

• #101 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  We found that duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] These findings not only confirm but extend previous case reports and indicate that cholecystectomy significantly increases the risk of duodenogastric bile reflux and causes more severe symptoms of functional dyspepsia, necessitating a need for stronger analgesia in many patients. […] Irrespective of the predisposing factors, prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance. […] The degree and duration of bile exposure that is needed to develop gastropathy is not fully understood, but once developed it manifests as gastric mucosal edema and hyperemia along with symptoms of functional dyspepsia.

• #102 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/view.html?uid=1687&vmd=Full

  We found that duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] These findings not only confirm but extend previous case reports and indicate that cholecystectomy significantly increases the risk of duodenogastric bile reflux and causes more severe symptoms of functional dyspepsia, necessitating a need for stronger analgesia in many patients. […] Irrespective of the predisposing factors, prolonged and excessive bile reflux into the stomach can cause direct chemical injury to the mucosa resulting in mucin depletion and hydrogen ion influx into the enterocytes and decreased transepithelial resistance. […] The degree and duration of bile exposure that is needed to develop gastropathy is not fully understood, but once developed it manifests as gastric mucosal edema and hyperemia along with symptoms of functional dyspepsia.

• #103 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/journal/view.html?spage=400&volume=27&number=3

  The findings of erythematous mucosa on endoscopy together with chemical gastropathy on biopsy is not uncommon, and has been reported in 15.0% of routine screening endoscopy procedures. […] Duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] Cholecystectomy was a significant predisposing risk factor for the development of bile reflux, and was associated with more severe gastrointestinal symptoms, and use of narcotic pain medications. […] The presence of bile gastritis during an upper endoscopy together with chemical gastropathy identified by histology is essential for a diagnosis.

• #104 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/journal/view.html?spage=400&volume=27&number=3

  The findings of erythematous mucosa on endoscopy together with chemical gastropathy on biopsy is not uncommon, and has been reported in 15.0% of routine screening endoscopy procedures. […] Duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] Cholecystectomy was a significant predisposing risk factor for the development of bile reflux, and was associated with more severe gastrointestinal symptoms, and use of narcotic pain medications. […] The presence of bile gastritis during an upper endoscopy together with chemical gastropathy identified by histology is essential for a diagnosis.

• #105 Bile Reflux Gastropathy and Functional Dyspepsia

  https://www.jnmjournal.org/journal/view.html?spage=400&volume=27&number=3

  The findings of erythematous mucosa on endoscopy together with chemical gastropathy on biopsy is not uncommon, and has been reported in 15.0% of routine screening endoscopy procedures. […] Duodenogastric bile reflux significantly contributed to the pathogenesis of symptoms in over one third of patients with chronic functional dyspepsia. […] Cholecystectomy was a significant predisposing risk factor for the development of bile reflux, and was associated with more severe gastrointestinal symptoms, and use of narcotic pain medications. […] The presence of bile gastritis during an upper endoscopy together with chemical gastropathy identified by histology is essential for a diagnosis.

• #106 Does Bile Reflux Increase Following Cholecystectomy? – Houston Heartburn and Reflux Center

  https://houstonheartburn.com/does-bile-reflux-increase-following-cholecystectomy/

  “Gastroesophageal Mucosal Injury after Cholecystectomy: An Indication for Surveillance?” is a new study published by T. Walsh et al in the current issue of JACS (Journal of the American College of Surgeons). The authors evaluate the incidence of stomach bile pooling detected by endoscopy in patients before and after cholecystectomy. They further measure the bile reflux index, cellular proliferation marker Ki67 and tumor-suppressor gene p53 in biopsies taken from the gastro-esophageal junction and gastric antrum. The analysis show that cholecystectomy increases the incidence of bile reflux and bile induced damage of gastric and esophageal mucosa. Chronic bile induced esophagitis and gastritis increase the incidence of gastric and esophageal cancer. The role of bile reflux in the pathogenesis of Barrett’s esophagus is well established and 10% of patients with Barrett’s esophagus develop esophageal adenocarcinoma. […] This study shows that cholecystectomy increases the risk of bile reflux and esophago-gastric mucosa injury. I suspect the risk of bile reflux and mucosal injury is highest in GERD patients who undergo an unindicated cholecystectomy.

• #107 Bile Reflux: Clinical Considerations – Gastroenterology Advisor

  https://www.gastroenterologyadvisor.com/features/tips-for-distinguishing-and-treating-biliary-reflux/

  Therefore, patients with evidence of bile reflux should be considered for more aggressive therapy, in the hopes of potentially preventing negative sequelae such as BE. […] It is important to note that this study found that a history of CCY was associated with bile reflux, which is most likely secondary to the unregulated and more pronounced delivery of bile into the duodenum. […] Increased levels of bile could reduce duodenal motility, making patients more prone to develop bile reflux. […] The authors concluded that duodeno-gastric bile reflux was present in at least 1/3 of patients with functional dyspepsia.

• #108 Bile reflux – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bile-reflux/symptoms-causes/syc-20370115

  Bile reflux occurs when bile a digestive liquid produced in your liver backs up (refluxes) into your stomach and, in some cases, into the tube that connects your mouth and stomach (esophagus). […] Unlike gastric acid reflux, bile reflux can’t be completely controlled by changes in diet or lifestyle. Treatment involves medications or, in severe cases, surgery. […] In cases of bile reflux, the valve doesn’t close properly, and bile washes back into the stomach. This can lead to inflammation of the stomach lining (bile reflux gastritis). […] Bile and stomach acid can reflux into the esophagus when another muscular valve, the lower esophageal sphincter, doesn’t work properly. […] Bile reflux may be caused by: […] Stomach surgery, including total or partial removal of the stomach and gastric bypass surgery for weight loss, is responsible for most bile reflux.

• #109 Biliary reflux after bariatric surgery and after gastroesophageal surgery for gastroesophageal reflux disease – Marabotto – Digestive Medicine Research

  https://dmr.amegroups.org/article/view/9258/html

  Biliary reflux refers to the ascent of duodenal fluid, biliary and pancreatic secretions into the stomach and esophagus. It is a primitive phenomenon or it can be secondary to gastric or biliary surgery. In particular, biliary reflux seems common after bariatric surgeries with, however, unknown incidence. Current data show that the prevalence of biliary reflux was higher after minigastric bypass as compared to the other bariatric surgeries. Nevertheless, biliary reflux resulted to be a relevant risk factor for the development of reflux-related complications, such as erosive esophagitis and Barrett esophagus, and its persistence over time seems to be an independent risk factor for gastric cancer. The likely mechanism of bile acids inducing esophageal symptoms is the release of intercellular mediators via damage to lipid membranes. The reflux of duodenal contents via the stomach into the esophagus is also able to induce mucosal injury and this has been shown both in animals and in humans. Conjugated bile acids enter the mucosal cells in unionized form (predominant form at low pH) through the lipophilic lipid membrane and then accumulate as intracellular ionization results in entrapment. This high concentration of bile acids causes intracellular damage by the dissolution of cell membranes and tight junctions. The pathogenetic role in the esophagus of duodenal contents consisting of bilirubin, bile acids and pancreatic enzymes have been confirmed by the development of erosive esophagitis in patients undergoing total gastrectomy or in those with achlorhydria. Moreover, esophageal exposure to both acid and DGER was shown to be present in 100% of patients with complicated Barretts esophagus, 89% of uncomplicated Barretts esophagus, 75% of erosive esophagitis and 50% of NERD by using combined 24-hour pH and Bilitec monitoring. These latter findings by Vaezi et al. confirm that there is a synergy between acid and DGER, which contributes to induce not only the presence but also the severity of esophageal mucosal lesions. Biliary reflux could be easily misdiagnosed or misinterpreted, but considering the certified involvement in the pathogenesis of precancerous lesions, its evaluation is pivotal. Moreover, other studies have documented that bile reflux is an independent risk factor for gastric cancer, thus highlighting the importance of its assessment.

• #110 Bile reflux after bariatric surgery | Cirugía Española (English Edition)

  https://www.elsevier.es/es-revista-cirugia-espanola-english-edition–436-articulo-bile-reflux-after-bariatric-surgery-S2173507723002235

  The growing epidemic of obesity and the increase in weight loss surgery has led to a resurgence of interest in biliary reflux because anatomical alterations may be refluxogenic. […] Although obesity is an independent risk factor for the development of gastro-oesophageal reflux, the anatomical alterations of bariatric surgery may also be refluxogenic. Duodenal contents (bile, bicarbonate and pancreatic enzymes) may reflux into the stomach and oesophagus, which is called duodenogastro-oesophageal reflux (DGOR) or biliary reflux. […] It is well documented that bile acids, together with gastric acid, contribute to reflux-type symptoms (heartburn, regurgitation, etc.), erosive oesophagitis and Barrett’s oesophagus. […] Patients with more advanced oesophageal lesions have a higher degree of duodenal reflux than those with simpler lesions. It has been demonstrated in animal models and in vitro that there is more Barrett’s and dysplasia with duodenal reflux.

• #111 Bile or Acid Reflux Post One-Anastomosis Gastric Bypass: What Must We Do? Still an Unsolved Enigma

  https://www.mdpi.com/2077-0383/11/12/3346

  Bile reflux post OAGB is a significant concern, with the main hypothesis to date being that of bile origin. Its role in the genesis of gastritis, esophagitis, anastomotic ulcer, as well as gastric and esophageal cancer has been pointed out in several studies. To begin with, it is essential to understand the mechanism of post-OAGB bile reflux occurrence, as there is confusion in the literature regarding its definition. It is mandatory to distinguish between reflux of bile into the gastric pouch and gastroesophageal reflux. The mechanism of bile reflux into the gastric pouch is easily conceived. Due to the surgical technique, the gastrojejunal anastomosis is permanently exposed to bile flow. The absence of an anatomical barrier, such as a sphincter at the gastrojejunal junction, may allow the passage of bile into the gastric pouch and could promote the development of gastritis and marginal ulcer. This mechanism was highlighted in a recent study on bile reflux scintigraphy showing that transient bile reflux post OAGB is common in the gastric tube, but not in the esophagus.

• #112 Bile Reflux: Clinical Considerations – Gastroenterology Advisor

  https://www.gastroenterologyadvisor.com/features/tips-for-distinguishing-and-treating-biliary-reflux/

  Bile reflux occurs when the bile secreted into the duodenum moves retrograde into the stomach and potentially into the esophagus. […] In certain patients with bile reflux, it has been postulated that a weak or widely patent pylorus could predispose patients to this condition. […] Bile reflux may also be more common in patients with motility disorders, especially in those whose gastric or duodenal motility is reduced, including certain patients with type 2 diabetes mellitus or those taking chronic opioid medications. […] Patients who have undergone gastric surgeries where the pylorus is bypassed or disrupted may be predisposed to developing bile reflux as well. […] Bile reflux is typically alkaline in nature, compared with the acidic environment found in the stomach. […] Despite this difference in pH, patients can experience similar symptoms, making bile reflux and GERD difficult to distinguish.

• #113 Bile reflux after bariatric surgery | Cirugía Española (English Edition)

  https://www.elsevier.es/es-revista-cirugia-espanola-english-edition–436-articulo-bile-reflux-after-bariatric-surgery-S2173507723002235

  Bile reflux into the oesophagus is a complication that occurs in a variable percentage of cases in the various published series. […] The relatively low frequency and low severity of biliary reflux can be explained by the presence of a wide anastomosis, greater than 3cm in diameter, which allows easy and rapid gastric emptying, making it a low-pressure system in which intragastric pressure and the oesophagogastric pressure gradient are reduced. […] Duodenogastric reflux can occur physiologically and is of minimal concern, while oesophageal bile has the potential to be associated with mucosal damage. Exposure of the oesophageal mucosa to bile acids increases epithelial permeability and promotes intracellular translocation of bile acids. […] Despite the known histopathological links between oesophageal mucosal exposure to bile and carcinogenesis, only two cases of gastric pouch/distal oesophageal malignancy have been described in 20 years since the advent of OAGB.

• #114 Bile reflux after bariatric surgery | Cirugía Española (English Edition)

  https://www.elsevier.es/es-revista-cirugia-espanola-english-edition–436-articulo-bile-reflux-after-bariatric-surgery-S2173507723002235

  Bile reflux into the oesophagus is a complication that occurs in a variable percentage of cases in the various published series. […] The relatively low frequency and low severity of biliary reflux can be explained by the presence of a wide anastomosis, greater than 3cm in diameter, which allows easy and rapid gastric emptying, making it a low-pressure system in which intragastric pressure and the oesophagogastric pressure gradient are reduced. […] Duodenogastric reflux can occur physiologically and is of minimal concern, while oesophageal bile has the potential to be associated with mucosal damage. Exposure of the oesophageal mucosa to bile acids increases epithelial permeability and promotes intracellular translocation of bile acids. […] Despite the known histopathological links between oesophageal mucosal exposure to bile and carcinogenesis, only two cases of gastric pouch/distal oesophageal malignancy have been described in 20 years since the advent of OAGB.

• #115 Acid and Bile Reflux following Stomach Surgery – Houston Heartburn and Reflux Center

  https://houstonheartburn.com/acid-and-bile-reflux-following-stomach-surgery/

  Results showed increased acid and alkaline reflux, and distal esophagitis in Billroth II patients only. […] Furthermore, gastric pressure in Billroth II patients significantly dropped compared to mini-gastric bypass patients favoring bile reflux across the gastro-jejunostomy. […] The authors observe that bile stasis in the gastric remnant leads to deterioration of the anti-reflux barrier and increased incidence of GERD in the setting of classical Billroth II reconstruction. […] There is no doubt in my mind that gastric fundus resection, similar to plication, alters the anti-reflux barrier. […] Therefore, it is no surprise to me that a Billroth II reconstruction in the setting of mini-gastric bypass is associated with lower GERD and bile stasis incidence when compared to a classic Billroth II. […] It does point however, to an important concept in GERD pathophysiology: the stomach and in particular the gastric fundus plays an important role in the acid reflux barrier and pathogenesis of acid reflux disease.

• #116 Acid and Bile Reflux following Stomach Surgery – Houston Heartburn and Reflux Center

  https://houstonheartburn.com/acid-and-bile-reflux-following-stomach-surgery/

  Results showed increased acid and alkaline reflux, and distal esophagitis in Billroth II patients only. […] Furthermore, gastric pressure in Billroth II patients significantly dropped compared to mini-gastric bypass patients favoring bile reflux across the gastro-jejunostomy. […] The authors observe that bile stasis in the gastric remnant leads to deterioration of the anti-reflux barrier and increased incidence of GERD in the setting of classical Billroth II reconstruction. […] There is no doubt in my mind that gastric fundus resection, similar to plication, alters the anti-reflux barrier. […] Therefore, it is no surprise to me that a Billroth II reconstruction in the setting of mini-gastric bypass is associated with lower GERD and bile stasis incidence when compared to a classic Billroth II. […] It does point however, to an important concept in GERD pathophysiology: the stomach and in particular the gastric fundus plays an important role in the acid reflux barrier and pathogenesis of acid reflux disease.

• #117 Bile or Acid Reflux Post One-Anastomosis Gastric Bypass: What Must We Do? Still an Unsolved Enigma

  https://www.mdpi.com/2077-0383/11/12/3346

  Bile reflux post OAGB is a significant concern, with the main hypothesis to date being that of bile origin. Its role in the genesis of gastritis, esophagitis, anastomotic ulcer, as well as gastric and esophageal cancer has been pointed out in several studies. To begin with, it is essential to understand the mechanism of post-OAGB bile reflux occurrence, as there is confusion in the literature regarding its definition. It is mandatory to distinguish between reflux of bile into the gastric pouch and gastroesophageal reflux. The mechanism of bile reflux into the gastric pouch is easily conceived. Due to the surgical technique, the gastrojejunal anastomosis is permanently exposed to bile flow. The absence of an anatomical barrier, such as a sphincter at the gastrojejunal junction, may allow the passage of bile into the gastric pouch and could promote the development of gastritis and marginal ulcer. This mechanism was highlighted in a recent study on bile reflux scintigraphy showing that transient bile reflux post OAGB is common in the gastric tube, but not in the esophagus.

• #118 Bile reflux after bariatric surgery | Cirugía Española (English Edition)

  https://www.elsevier.es/es-revista-cirugia-espanola-english-edition–436-articulo-bile-reflux-after-bariatric-surgery-S2173507723002235

  Recent trials that have attempted to directly treat bile as a component of gastro-oesophageal reflux disease (GORD) have demonstrated an improvement in symptoms and lesions in these patients. […] A new therapy, called IW-3718 (Colesevelam), binds and neutralises bile in the stomach, decreasing the volume of reflux and improving endoscopic imaging in 87% of cases, while also increasing muscle tissue relaxation. […] DGOR increases the prevalence of more advanced oesophageal lesions and we must continue to advance future therapies to address this reflux. […] After OAGB surgery a small amount of bile may be transiently present in the stomach in about 50% of cases, leading to a mild chronic gastritis marked by the presence of foveolar hyperplasia, a specific marker of bile contact with the gastric mucosa.

• #119 Bile or Acid Reflux Post One-Anastomosis Gastric Bypass: What Must We Do? Still an Unsolved Enigma

  https://www.mdpi.com/2077-0383/11/12/3346

  Bile reflux post OAGB is a significant concern, with the main hypothesis to date being that of bile origin. Its role in the genesis of gastritis, esophagitis, anastomotic ulcer, as well as gastric and esophageal cancer has been pointed out in several studies. To begin with, it is essential to understand the mechanism of post-OAGB bile reflux occurrence, as there is confusion in the literature regarding its definition. It is mandatory to distinguish between reflux of bile into the gastric pouch and gastroesophageal reflux. The mechanism of bile reflux into the gastric pouch is easily conceived. Due to the surgical technique, the gastrojejunal anastomosis is permanently exposed to bile flow. The absence of an anatomical barrier, such as a sphincter at the gastrojejunal junction, may allow the passage of bile into the gastric pouch and could promote the development of gastritis and marginal ulcer. This mechanism was highlighted in a recent study on bile reflux scintigraphy showing that transient bile reflux post OAGB is common in the gastric tube, but not in the esophagus.

• #120 Bile or Acid Reflux Post One-Anastomosis Gastric Bypass: What Must We Do? Still an Unsolved Enigma

  https://www.mdpi.com/2077-0383/11/12/3346

  Bile reflux post OAGB is a significant concern, with the main hypothesis to date being that of bile origin. Its role in the genesis of gastritis, esophagitis, anastomotic ulcer, as well as gastric and esophageal cancer has been pointed out in several studies. To begin with, it is essential to understand the mechanism of post-OAGB bile reflux occurrence, as there is confusion in the literature regarding its definition. It is mandatory to distinguish between reflux of bile into the gastric pouch and gastroesophageal reflux. The mechanism of bile reflux into the gastric pouch is easily conceived. Due to the surgical technique, the gastrojejunal anastomosis is permanently exposed to bile flow. The absence of an anatomical barrier, such as a sphincter at the gastrojejunal junction, may allow the passage of bile into the gastric pouch and could promote the development of gastritis and marginal ulcer. This mechanism was highlighted in a recent study on bile reflux scintigraphy showing that transient bile reflux post OAGB is common in the gastric tube, but not in the esophagus.

• #121 Bile or Acid Reflux Post One-Anastomosis Gastric Bypass: What Must We Do? Still an Unsolved Enigma

  https://www.mdpi.com/2077-0383/11/12/3346

  Bile reflux post OAGB is a significant concern, with the main hypothesis to date being that of bile origin. Its role in the genesis of gastritis, esophagitis, anastomotic ulcer, as well as gastric and esophageal cancer has been pointed out in several studies. To begin with, it is essential to understand the mechanism of post-OAGB bile reflux occurrence, as there is confusion in the literature regarding its definition. It is mandatory to distinguish between reflux of bile into the gastric pouch and gastroesophageal reflux. The mechanism of bile reflux into the gastric pouch is easily conceived. Due to the surgical technique, the gastrojejunal anastomosis is permanently exposed to bile flow. The absence of an anatomical barrier, such as a sphincter at the gastrojejunal junction, may allow the passage of bile into the gastric pouch and could promote the development of gastritis and marginal ulcer. This mechanism was highlighted in a recent study on bile reflux scintigraphy showing that transient bile reflux post OAGB is common in the gastric tube, but not in the esophagus.

• #122 Bile or Acid Reflux Post One-Anastomosis Gastric Bypass: What Must We Do? Still an Unsolved Enigma

  https://www.mdpi.com/2077-0383/11/12/3346

  Bile reflux post OAGB is a significant concern, with the main hypothesis to date being that of bile origin. Its role in the genesis of gastritis, esophagitis, anastomotic ulcer, as well as gastric and esophageal cancer has been pointed out in several studies. To begin with, it is essential to understand the mechanism of post-OAGB bile reflux occurrence, as there is confusion in the literature regarding its definition. It is mandatory to distinguish between reflux of bile into the gastric pouch and gastroesophageal reflux. The mechanism of bile reflux into the gastric pouch is easily conceived. Due to the surgical technique, the gastrojejunal anastomosis is permanently exposed to bile flow. The absence of an anatomical barrier, such as a sphincter at the gastrojejunal junction, may allow the passage of bile into the gastric pouch and could promote the development of gastritis and marginal ulcer. This mechanism was highlighted in a recent study on bile reflux scintigraphy showing that transient bile reflux post OAGB is common in the gastric tube, but not in the esophagus.

• #123 Bile reflux after bariatric surgery | Cirugía Española (English Edition)

  https://www.elsevier.es/es-revista-cirugia-espanola-english-edition–436-articulo-bile-reflux-after-bariatric-surgery-S2173507723002235

  Recent trials that have attempted to directly treat bile as a component of gastro-oesophageal reflux disease (GORD) have demonstrated an improvement in symptoms and lesions in these patients. […] A new therapy, called IW-3718 (Colesevelam), binds and neutralises bile in the stomach, decreasing the volume of reflux and improving endoscopic imaging in 87% of cases, while also increasing muscle tissue relaxation. […] DGOR increases the prevalence of more advanced oesophageal lesions and we must continue to advance future therapies to address this reflux. […] After OAGB surgery a small amount of bile may be transiently present in the stomach in about 50% of cases, leading to a mild chronic gastritis marked by the presence of foveolar hyperplasia, a specific marker of bile contact with the gastric mucosa.

• #124 Bile reflux after bariatric surgery | Cirugía Española (English Edition)

  https://www.elsevier.es/es-revista-cirugia-espanola-english-edition–436-articulo-bile-reflux-after-bariatric-surgery-S2173507723002235

  Recent trials that have attempted to directly treat bile as a component of gastro-oesophageal reflux disease (GORD) have demonstrated an improvement in symptoms and lesions in these patients. […] A new therapy, called IW-3718 (Colesevelam), binds and neutralises bile in the stomach, decreasing the volume of reflux and improving endoscopic imaging in 87% of cases, while also increasing muscle tissue relaxation. […] DGOR increases the prevalence of more advanced oesophageal lesions and we must continue to advance future therapies to address this reflux. […] After OAGB surgery a small amount of bile may be transiently present in the stomach in about 50% of cases, leading to a mild chronic gastritis marked by the presence of foveolar hyperplasia, a specific marker of bile contact with the gastric mucosa.

• #125 Bile reflux after bariatric surgery | Cirugía Española (English Edition)

  https://www.elsevier.es/es-revista-cirugia-espanola-english-edition–436-articulo-bile-reflux-after-bariatric-surgery-S2173507723002235

  Recent trials that have attempted to directly treat bile as a component of gastro-oesophageal reflux disease (GORD) have demonstrated an improvement in symptoms and lesions in these patients. […] A new therapy, called IW-3718 (Colesevelam), binds and neutralises bile in the stomach, decreasing the volume of reflux and improving endoscopic imaging in 87% of cases, while also increasing muscle tissue relaxation. […] DGOR increases the prevalence of more advanced oesophageal lesions and we must continue to advance future therapies to address this reflux. […] After OAGB surgery a small amount of bile may be transiently present in the stomach in about 50% of cases, leading to a mild chronic gastritis marked by the presence of foveolar hyperplasia, a specific marker of bile contact with the gastric mucosa.

• #126 Histological features of the gastric mucosa in children with primary bile reflux gastritis | World Journal of Surgical Oncology | Full Text

  https://wjso.biomedcentral.com/articles/10.1186/1477-7819-10-27

  Bile reflux is one of the primary factors involved in the pathogenesis of gastric mucosal lesions in patients with chronic gastritis; however, little is known about the exact histological features of bile reflux and its contributions to gastric mucosal lesions in this disease, especially in children with primary bile reflux gastritis (BRG). […] Foveolar hyperplasia was associated with the severity of bile reflux, suggesting that it is a histological feature of primary BRG in children, while vascular congestion may be a protective factor. […] Bile reflux is thought to be associated with chronic inflammation of the gastric mucosa, lamina propria edema, foveolar hyperplasia, antral atrophy, and intestinal metaplasia. […] Foveolar hyperplasia was a risk factor for patients with bile reflux, and vascular congestion was a protective factor. […] In conclusion, foveolar hyperplasia is associated with the degree of bile reflux and may serve as the characteristic histological change of primary BRG in children.

• #127 Histological features of the gastric mucosa in children with primary bile reflux gastritis | World Journal of Surgical Oncology | Full Text

  https://wjso.biomedcentral.com/articles/10.1186/1477-7819-10-27

  Bile reflux is one of the primary factors involved in the pathogenesis of gastric mucosal lesions in patients with chronic gastritis; however, little is known about the exact histological features of bile reflux and its contributions to gastric mucosal lesions in this disease, especially in children with primary bile reflux gastritis (BRG). […] Foveolar hyperplasia was associated with the severity of bile reflux, suggesting that it is a histological feature of primary BRG in children, while vascular congestion may be a protective factor. […] Bile reflux is thought to be associated with chronic inflammation of the gastric mucosa, lamina propria edema, foveolar hyperplasia, antral atrophy, and intestinal metaplasia. […] Foveolar hyperplasia was a risk factor for patients with bile reflux, and vascular congestion was a protective factor. […] In conclusion, foveolar hyperplasia is associated with the degree of bile reflux and may serve as the characteristic histological change of primary BRG in children.

• #128 Histological features of the gastric mucosa in children with primary bile reflux gastritis | World Journal of Surgical Oncology | Full Text

  https://wjso.biomedcentral.com/articles/10.1186/1477-7819-10-27

  Bile reflux is one of the primary factors involved in the pathogenesis of gastric mucosal lesions in patients with chronic gastritis; however, little is known about the exact histological features of bile reflux and its contributions to gastric mucosal lesions in this disease, especially in children with primary bile reflux gastritis (BRG). […] Foveolar hyperplasia was associated with the severity of bile reflux, suggesting that it is a histological feature of primary BRG in children, while vascular congestion may be a protective factor. […] Bile reflux is thought to be associated with chronic inflammation of the gastric mucosa, lamina propria edema, foveolar hyperplasia, antral atrophy, and intestinal metaplasia. […] Foveolar hyperplasia was a risk factor for patients with bile reflux, and vascular congestion was a protective factor. […] In conclusion, foveolar hyperplasia is associated with the degree of bile reflux and may serve as the characteristic histological change of primary BRG in children.

• #129 Histological features of the gastric mucosa in children with primary bile reflux gastritis | World Journal of Surgical Oncology | Full Text

  https://wjso.biomedcentral.com/articles/10.1186/1477-7819-10-27

  Bile reflux is one of the primary factors involved in the pathogenesis of gastric mucosal lesions in patients with chronic gastritis; however, little is known about the exact histological features of bile reflux and its contributions to gastric mucosal lesions in this disease, especially in children with primary bile reflux gastritis (BRG). […] Foveolar hyperplasia was associated with the severity of bile reflux, suggesting that it is a histological feature of primary BRG in children, while vascular congestion may be a protective factor. […] Bile reflux is thought to be associated with chronic inflammation of the gastric mucosa, lamina propria edema, foveolar hyperplasia, antral atrophy, and intestinal metaplasia. […] Foveolar hyperplasia was a risk factor for patients with bile reflux, and vascular congestion was a protective factor. […] In conclusion, foveolar hyperplasia is associated with the degree of bile reflux and may serve as the characteristic histological change of primary BRG in children.

• #130 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. […] To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. […] Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). […] Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. […] In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. […] In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface.

• #131 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. […] To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. […] Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). […] Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. […] In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. […] In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface.

• #132 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. […] To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. […] Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). […] Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. […] In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. […] In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface.

• #133 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. […] To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. […] Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). […] Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. […] In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. […] In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface.

• #134 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. […] To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. […] Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). […] Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. […] In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. […] In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface.

• #135 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. […] To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. […] Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). […] Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. […] In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. […] In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface.

• #136 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD. […] In patients with intact gastric acid production, the pyloric antrum mucous layer may have the optimal bile concentration to direct H. pylori to the epithelial surface and thus enable H. pylori colonization, while the stomach body may be less optimal for H. pylori colonization. […] Therefore, in the distal stomach, the high concentration of soluble bile acids likely acts as a bactericide or chemorepellent for H. pylori, and chemotactic gradients with plasma components are not formed to direct the H. pylori toward the epithelial surface. […] In conclusion, interactions between bile acids, pH, and H. pylori seem to be associated with the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

• #137 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. […] To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. […] Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). […] Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. […] In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. […] In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface.

• #138 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD. […] In patients with intact gastric acid production, the pyloric antrum mucous layer may have the optimal bile concentration to direct H. pylori to the epithelial surface and thus enable H. pylori colonization, while the stomach body may be less optimal for H. pylori colonization. […] Therefore, in the distal stomach, the high concentration of soluble bile acids likely acts as a bactericide or chemorepellent for H. pylori, and chemotactic gradients with plasma components are not formed to direct the H. pylori toward the epithelial surface. […] In conclusion, interactions between bile acids, pH, and H. pylori seem to be associated with the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

• #139 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  The long-term use of proton pump inhibitors (PPIs) exacerbates corpus atrophic gastritis in patients with Helicobacter pylori (H. pylori) infection. […] To identify a potential mechanism for this change, we discuss interactions between pH, bile acids, and H. pylori. […] Duodenogastric reflux, which includes bile, occurs in healthy individuals, and bile reflux is increased in patients with gastroesophageal reflux disease (GERD). […] Thus, the soluble bile acid concentrations in the gastric contents of patients with GERD after continuous PPI therapy are considerably higher than that in those with intact acid production. […] In the distal stomach, the high concentration of soluble bile acids is likely to act as a bactericide or chemorepellent for H. pylori. […] In contrast, the mucous layer in the proximal stomach has an optimal bile concentration that forms chemotactic gradients with plasma components required to direct H. pylori to the epithelial surface.

• #140 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD. […] In patients with intact gastric acid production, the pyloric antrum mucous layer may have the optimal bile concentration to direct H. pylori to the epithelial surface and thus enable H. pylori colonization, while the stomach body may be less optimal for H. pylori colonization. […] Therefore, in the distal stomach, the high concentration of soluble bile acids likely acts as a bactericide or chemorepellent for H. pylori, and chemotactic gradients with plasma components are not formed to direct the H. pylori toward the epithelial surface. […] In conclusion, interactions between bile acids, pH, and H. pylori seem to be associated with the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

• #141 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD. […] In patients with intact gastric acid production, the pyloric antrum mucous layer may have the optimal bile concentration to direct H. pylori to the epithelial surface and thus enable H. pylori colonization, while the stomach body may be less optimal for H. pylori colonization. […] Therefore, in the distal stomach, the high concentration of soluble bile acids likely acts as a bactericide or chemorepellent for H. pylori, and chemotactic gradients with plasma components are not formed to direct the H. pylori toward the epithelial surface. […] In conclusion, interactions between bile acids, pH, and H. pylori seem to be associated with the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

• #142 Potential mechanism of corpus-predominant gastritis after PPI therapy in Helicobacter pylori-positive patients with GERD

  https://www.wjgnet.com/1007-9327/full/v20/i34/11962.htm

  H. pylori may then colonize in the stomach body rather than in the pyloric antrum, which may explain the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD. […] In patients with intact gastric acid production, the pyloric antrum mucous layer may have the optimal bile concentration to direct H. pylori to the epithelial surface and thus enable H. pylori colonization, while the stomach body may be less optimal for H. pylori colonization. […] Therefore, in the distal stomach, the high concentration of soluble bile acids likely acts as a bactericide or chemorepellent for H. pylori, and chemotactic gradients with plasma components are not formed to direct the H. pylori toward the epithelial surface. […] In conclusion, interactions between bile acids, pH, and H. pylori seem to be associated with the occurrence of corpus-predominant gastritis after PPI therapy in H. pylori-positive patients with GERD.

• #143 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  Bile reflux (BR) can influence the gastric environment by altering gastric acidity and possibly the gastric microbiota composition. […] Changes in microbial diversity in the gastric juice were associated with BR presence in the stomach. This result suggests that the degree of BR should be considered when studying the gastric juice microbiome. […] Bile reflux (BR) refers to the condition whereby duodenal contents, such as bile and pancreatic juice, are refluxed back into the stomach. […] Bile acid in the stomach can disrupt the mucosal barrier by dissolving the phospholipid layer in the epithelial membrane, inhibiting nitric oxide enzymes and the sodiumhydrogen exchanges in cells, stimulating histamine release from mast cells, and promoting the reverse diffusion of hydrogen ions. These changes can lead to intracellular DNA damage, apoptosis, mutation, and chronic inflammation of gastric mucosa.

• #144 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The current study demonstrated that the -diversity in the gastric juice microbiota was significantly lower in the patients with BR than those without BR. This may be due to the antibiotic effect of bile acid, which increases membrane disruption and leakage of cellular contents and induces DNA damage, protein misfolding, and oxidative stress. […] The bile acid antimicrobial effect is concentration-dependent, while its sensitivity varies depending on the bacterias characteristics, such as efflux pumps, cell wall modification, and an ability to express bile acid exporters or enzymes. […] The microbial compositional comparison using beta-diversity analysis also showed significant differences according to BR, histological phenotype, and H. pylori infection, although no significant differences were observed between grades in the same categories (i.e., BR1 vs. BR2; LGD vs. EGC).

• #145 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The current study demonstrated that the -diversity in the gastric juice microbiota was significantly lower in the patients with BR than those without BR. This may be due to the antibiotic effect of bile acid, which increases membrane disruption and leakage of cellular contents and induces DNA damage, protein misfolding, and oxidative stress. […] The bile acid antimicrobial effect is concentration-dependent, while its sensitivity varies depending on the bacterias characteristics, such as efflux pumps, cell wall modification, and an ability to express bile acid exporters or enzymes. […] The microbial compositional comparison using beta-diversity analysis also showed significant differences according to BR, histological phenotype, and H. pylori infection, although no significant differences were observed between grades in the same categories (i.e., BR1 vs. BR2; LGD vs. EGC).

• #146 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The current study demonstrated that the -diversity in the gastric juice microbiota was significantly lower in the patients with BR than those without BR. This may be due to the antibiotic effect of bile acid, which increases membrane disruption and leakage of cellular contents and induces DNA damage, protein misfolding, and oxidative stress. […] The bile acid antimicrobial effect is concentration-dependent, while its sensitivity varies depending on the bacterias characteristics, such as efflux pumps, cell wall modification, and an ability to express bile acid exporters or enzymes. […] The microbial compositional comparison using beta-diversity analysis also showed significant differences according to BR, histological phenotype, and H. pylori infection, although no significant differences were observed between grades in the same categories (i.e., BR1 vs. BR2; LGD vs. EGC).

• #147 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The current study demonstrated that the -diversity in the gastric juice microbiota was significantly lower in the patients with BR than those without BR. This may be due to the antibiotic effect of bile acid, which increases membrane disruption and leakage of cellular contents and induces DNA damage, protein misfolding, and oxidative stress. […] The bile acid antimicrobial effect is concentration-dependent, while its sensitivity varies depending on the bacterias characteristics, such as efflux pumps, cell wall modification, and an ability to express bile acid exporters or enzymes. […] The microbial compositional comparison using beta-diversity analysis also showed significant differences according to BR, histological phenotype, and H. pylori infection, although no significant differences were observed between grades in the same categories (i.e., BR1 vs. BR2; LGD vs. EGC).

• #148 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The current study demonstrated that the -diversity in the gastric juice microbiota was significantly lower in the patients with BR than those without BR. This may be due to the antibiotic effect of bile acid, which increases membrane disruption and leakage of cellular contents and induces DNA damage, protein misfolding, and oxidative stress. […] The bile acid antimicrobial effect is concentration-dependent, while its sensitivity varies depending on the bacterias characteristics, such as efflux pumps, cell wall modification, and an ability to express bile acid exporters or enzymes. […] The microbial compositional comparison using beta-diversity analysis also showed significant differences according to BR, histological phenotype, and H. pylori infection, although no significant differences were observed between grades in the same categories (i.e., BR1 vs. BR2; LGD vs. EGC).

• #149 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The current study demonstrated that the -diversity in the gastric juice microbiota was significantly lower in the patients with BR than those without BR. This may be due to the antibiotic effect of bile acid, which increases membrane disruption and leakage of cellular contents and induces DNA damage, protein misfolding, and oxidative stress. […] The bile acid antimicrobial effect is concentration-dependent, while its sensitivity varies depending on the bacterias characteristics, such as efflux pumps, cell wall modification, and an ability to express bile acid exporters or enzymes. […] The microbial compositional comparison using beta-diversity analysis also showed significant differences according to BR, histological phenotype, and H. pylori infection, although no significant differences were observed between grades in the same categories (i.e., BR1 vs. BR2; LGD vs. EGC).

• #150 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The current study demonstrated that the -diversity in the gastric juice microbiota was significantly lower in the patients with BR than those without BR. This may be due to the antibiotic effect of bile acid, which increases membrane disruption and leakage of cellular contents and induces DNA damage, protein misfolding, and oxidative stress. […] The bile acid antimicrobial effect is concentration-dependent, while its sensitivity varies depending on the bacterias characteristics, such as efflux pumps, cell wall modification, and an ability to express bile acid exporters or enzymes. […] The microbial compositional comparison using beta-diversity analysis also showed significant differences according to BR, histological phenotype, and H. pylori infection, although no significant differences were observed between grades in the same categories (i.e., BR1 vs. BR2; LGD vs. EGC).

• #151 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The abundances of Streptococcus and Lancefielfdella were positively correlated with almost all bile acid components. In addition, the abundances of Solobacterium, Veillonella, and Schaalia were positively correlated with the primary unconjugated bile acids (i.e., CA, CDCA). […] These findings highlight the importance of considering the impact of BR when investigating gastric microbiota.

• #152 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The abundances of Streptococcus and Lancefielfdella were positively correlated with almost all bile acid components. In addition, the abundances of Solobacterium, Veillonella, and Schaalia were positively correlated with the primary unconjugated bile acids (i.e., CA, CDCA). […] These findings highlight the importance of considering the impact of BR when investigating gastric microbiota.

• #153 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The abundances of Streptococcus and Lancefielfdella were positively correlated with almost all bile acid components. In addition, the abundances of Solobacterium, Veillonella, and Schaalia were positively correlated with the primary unconjugated bile acids (i.e., CA, CDCA). […] These findings highlight the importance of considering the impact of BR when investigating gastric microbiota.

• #154 Effect of bile reflux on gastric juice microbiota in patients with different histology phenotypes | Gut Pathogens | Full Text

  https://gutpathogens.biomedcentral.com/articles/10.1186/s13099-024-00619-7

  The abundances of Streptococcus and Lancefielfdella were positively correlated with almost all bile acid components. In addition, the abundances of Solobacterium, Veillonella, and Schaalia were positively correlated with the primary unconjugated bile acids (i.e., CA, CDCA). […] These findings highlight the importance of considering the impact of BR when investigating gastric microbiota.

• #155 The relationship between bile reflux and common bile duct diameter after cholecystectomy: a clinical case-control study

  https://www.scielo.org.mx/scielo.php?pid=S2444-054X2023000100009&script=sci_arttext

  The present study aims to investigate the relationship between bile reflux (BR) and diameter of the common bile duct (CBD) in patients after cholecystectomy. […] We believe that CBD diameter may be a predictive factor in the detection of BR after cholecystectomy. […] The mechanism of BR formation is not clear. […] Following the studies showing that BR increased as a result of therapeutic biliary procedures, including cholecystectomy, attention was turned to the sphincter of Oddi. […] We observed in our study that BR was less common in cholecystectomy patients with increased CBD diameter. […] We are of the opinion that CBD diameter found 7 mm or below after cholecystectomy may be a predictive factor in the detection of BR.

• #156 The relationship between bile reflux and common bile duct diameter after cholecystectomy: a clinical case-control study

  https://www.scielo.org.mx/scielo.php?pid=S2444-054X2023000100009&script=sci_arttext

  The present study aims to investigate the relationship between bile reflux (BR) and diameter of the common bile duct (CBD) in patients after cholecystectomy. […] We believe that CBD diameter may be a predictive factor in the detection of BR after cholecystectomy. […] The mechanism of BR formation is not clear. […] Following the studies showing that BR increased as a result of therapeutic biliary procedures, including cholecystectomy, attention was turned to the sphincter of Oddi. […] We observed in our study that BR was less common in cholecystectomy patients with increased CBD diameter. […] We are of the opinion that CBD diameter found 7 mm or below after cholecystectomy may be a predictive factor in the detection of BR.

• #157 The relationship between bile reflux and common bile duct diameter after cholecystectomy: a clinical case-control study

  https://www.scielo.org.mx/scielo.php?pid=S2444-054X2023000100009&script=sci_arttext

  The present study aims to investigate the relationship between bile reflux (BR) and diameter of the common bile duct (CBD) in patients after cholecystectomy. […] We believe that CBD diameter may be a predictive factor in the detection of BR after cholecystectomy. […] The mechanism of BR formation is not clear. […] Following the studies showing that BR increased as a result of therapeutic biliary procedures, including cholecystectomy, attention was turned to the sphincter of Oddi. […] We observed in our study that BR was less common in cholecystectomy patients with increased CBD diameter. […] We are of the opinion that CBD diameter found 7 mm or below after cholecystectomy may be a predictive factor in the detection of BR.

• #158 The relationship between bile reflux and common bile duct diameter after cholecystectomy: a clinical case-control study

  https://www.scielo.org.mx/scielo.php?pid=S2444-054X2023000100009&script=sci_arttext

  The present study aims to investigate the relationship between bile reflux (BR) and diameter of the common bile duct (CBD) in patients after cholecystectomy. […] We believe that CBD diameter may be a predictive factor in the detection of BR after cholecystectomy. […] The mechanism of BR formation is not clear. […] Following the studies showing that BR increased as a result of therapeutic biliary procedures, including cholecystectomy, attention was turned to the sphincter of Oddi. […] We observed in our study that BR was less common in cholecystectomy patients with increased CBD diameter. […] We are of the opinion that CBD diameter found 7 mm or below after cholecystectomy may be a predictive factor in the detection of BR.

• #159 The relationship between bile reflux and common bile duct diameter after cholecystectomy: a clinical case-control study

  https://www.scielo.org.mx/scielo.php?pid=S2444-054X2023000100009&script=sci_arttext

  The present study aims to investigate the relationship between bile reflux (BR) and diameter of the common bile duct (CBD) in patients after cholecystectomy. […] We believe that CBD diameter may be a predictive factor in the detection of BR after cholecystectomy. […] The mechanism of BR formation is not clear. […] Following the studies showing that BR increased as a result of therapeutic biliary procedures, including cholecystectomy, attention was turned to the sphincter of Oddi. […] We observed in our study that BR was less common in cholecystectomy patients with increased CBD diameter. […] We are of the opinion that CBD diameter found 7 mm or below after cholecystectomy may be a predictive factor in the detection of BR.

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