Factors in the mechanism of diarrhea in bile acid malabsorption: Fecal pH—A key determinant

Abstract

High fecal aqueous dihydroxy bile acid concentrations are prerequisite for bile acid-induced diarrhea. This study identified factors which cause differences in the fecal aqueous phase dihydroxy bile acid concentrations among various conditions of bile acid malabsorption, and hence determine the presence or absence of bile acid enteropathy. The study, which included colonic intubations, was performed on control subjects as well as on groups of patients with similar degrees of bile acid malabsorption due to either various lengths of ileal and proximal colonic resections or jejunoileal bypass. The aqueous dihydroxy bile acid concentrations in stool were comparable to those in the colon. In all study groups, a high correlation was found between fecal pH and percent of fecal dihydroxy bile acids in aqueous solution. High fecal aqueous dihydroxy bile acid concentrations were present if bile acid malabsorption was associated with an alkaline fecal pH, as seen in small ileal resection with no or only moderate steatorrhea. The aqueous dihydroxy bile acid concentrations were low in bile acid malabsorption and severe steatorrhea due to large ileal resection, or jejunoileal bypass, in which the fecal pH was acidic. Fecal bile acids in jejunoileal bypdss Were considerably diluted to levels which would not be secretory, even at optimal (alkaline) pH and solubility. Binding of bile acids to the solid fecal phase was found to decrease the release of dihydroxy bile acids into the aqueous phase by about 20%. The bile acids in stool as well as in colonic contents were unconjugated and not sulfated. The increased fecal aqueous dihydroxy bile acids in small ileal resection consisted, predominantly, of either chenodeoxycholic acid or deoxycholic acid. This study indicates that fecal pH is the most important determinant of diarrhea in bile acid malabsorption due to ileal resection, whereas dilution of colonic contents is generally the determining factor in the diarrhea in bile acid malabsorption due to jejunoileal bypass. Also, for the first time, it has been shown that, not only chenodeoxycholic acid, but also deoxycholic acid, can be implicated in the pathogenesis of bile acid-induced diarrhea.