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

Dihydroxy bile acids increase mucosal permeability and bacterial uptake in human colon biopsies

“…DCA is quantitatively the main bile acid in faeces and accounts for approximately 65% of the total faecal bile acids. The proportions of primary bile acids excreted are generally low, but in conditions with accelerated transit time, diarrhoea or altered microflora the amount of CDCA can equal those of DCA [3] and the concentrations of bile acids in the aqueous phase of the faeces can exceed the millimolar range [4]. Thomas et al [5] compared caecal versus faecal bile acid concentrations in the unprepared colon and found cholic acid concentrations of up to 940 mmol/l in the aspirate of the right colon.…”

Exposure of intestinal epithelial cell HT29 to bile acids and ammonia enhances Mac-1-mediated neutrophil adhesion

“…In vivo concentrations of ammonia are 4-70 mM, and concentrations of bile acids are in millimolar ranges under disease conditions [9][10][11]19]. The present study revealed bile acids and ammonia exerted their actions on HT29 cells in micromolar ranges (> 10 mM).…”

“…Bile acids are end products of cholesterol metabolism, and participate in fat digestion in the gastrointestinal tract. In health, the majority of bile acids present in millimolar ranges during digestion is efficiently absorbed via both active and passive mechanisms by small intestine, and only a small fraction of bile acids escapes from enterohepatic circulation [8], resulting in the bile acid concentrations in the cecum being in micromolar ranges [9]. However, in patients with abnormal ileal absorption, bile acids are malabsorbed, and the increased fecal loss of bile acids induces a compensatory increase in bile acid biosynthesis in the liver.…”

“…Thus, increased amounts of bile acids pass into the colon under the diseased conditions. In fact, bile acids are markedly increased in the feces of patients with diarrhea [9][10][11]. Increased bile acids in colon are considered to influence intestinal epithelial functions and play a role in the pathogenesis of intestinal inflammation [12].…”

Mechanisms of Diarrhea

“…Moreover, the absence of the ileum contributes to diarrhea, with both the loss of absorptive capacity and loss of "ileal brake" [25]. Bile acids in the colon can cause diarrhea by several mechanisms: stimulating sodium and water secretion, inducing mucus secretion, increasing colon motility, stimulating defecation, and/or damaging the mucosa with decreased intestinal permeability [26][27][28].…”