Influence of pH on bile acid concentration in human, pig and commercial bile: Implications for 'alkaline' gastro-esophageal reflux

The relative pathogenetic role of bile acids and gastric acid in patients with reflux esophagitis are controversial. This is because bile acids cause esophageal mucosal injury in vitro but can frequently not be measured in aspirates of patients with acid gastro-esophageal reflux. This prompted us to investigate the pH dependent behaviour of natural bile acids using high performance liquid chromatography. Gallbladder bile of 12 humans and 16 pigs with a pH of 6 to 7 was titrated to a pH of 11 (NaOH) and to a pH of 1 (HCl). Acidification to a pH below 4 resulted in a marked decrease of all measured bile acids (p < 0.001) of the human and pig bile as quantified by means of high performance liquid chromatography. This correlated with precipitation which was not reversible. Commercially available bile acids did not precipitate and remained in solution with acid exposure. The clinical implications are twofold: (1) regurgitated bile acids may precipitate and become inactivated within an acidic gastric environment. Consequently, bile acids are rarely found in the esophagus of patients with an acid secreting stomach and predominant acid gastro-esophageal reflux. (2) In an alkaline environment, i.e. after gastrectomy or with acid suppression therapy, bile acids may reflux into the esophagus unprecipitated and may cause esophageal mucosal injury.