Bile Acid Diarrhea in Adults and Adolescents

Abstract

Background Bile acids are central to enterohepatic signaling pathways activated through natural receptors, farnesoid X receptor [FXR mediates synthesis of fibroblast growth factor‐19 (FGF‐19)], and G protein‐coupled bile acid receptor 1 (GPBAR1, also known as TGR5). Although bile acid diarrhea (BAD) is more commonly encountered in ileal resection or disease, there is evidence documenting “idiopathic” BAD in about 20% of adolescents and 30% of adults presenting with chronic, non‐bloody diarrhea often attributed to irritable bowel syndrome. Mechanism(s) leading to increased hepatic synthesis and colonic bile acid levels in “idiopathic” BAD include reduced synthesis of FGF‐19 by the ileal mucosa, or genetic variation in hepatocyte proteins klotho β and FGF receptor 4 (FGFR4) that mediate negative feedback of bile acid synthesis. Purpose: The objective of this review is to summarize the diagnosis of BAD in adults and adolescents. In addition to 75SeHCAT retention for diagnosis of BAD, studies have validated fasting serum 7αC4 and FGF‐19, respectively, by‐product and inhibitor of hepatic bile acid synthesis, as well as fecal bile acid measurements. These assays are widely available through reference laboratories, and they are being simplified (eg, measurement of primary fecal bile acids in a random stool sample). BAD has also been identified as a co‐factor contributing to persistent diarrhea in other diseases in remission including inflammatory bowel disease, microscopic colitis, celiac disease, and neuroendocrine tumors. In summary, advances in diagnosis of BAD provide opportunities for generalists and pediatric and adult gastroenterologists to provide targeted treatment for BAD presenting as chronic non‐bloody diarrhea.

Irritable bowel syndrome: treatment based on pathophysiology and biomarkers

“…The main secondary bile acids are lithocholic acid, deoxycholic acid and ursodeoxycholic acid. In the colon, bile acids cause increased secretion, increased mucosal permeability and stimulate motility (eg, high amplitude colonic contractions) 17. BAD affects both adolescents and adults 17 18…”

Diagnostic yield of colonoscopy for organic disease in irritable bowel syndrome and its risk factors: A meta‐analysis

“…Diagnosis of bile acid diarrhea is made on selenium homotaurocholic acid test (SeHCAT), which is not available in some countries. 49 Third,…”

“…We examined the data of included studies in our meta‐analysis, and only three studies provided the data for celiac disease making it insufficient for pooling. Diagnosis of bile acid diarrhea is made on selenium homotaurocholic acid test (SeHCAT), which is not available in some countries 49 . Third , diagnostic evaluation of IBS patients prior to colonoscopy was not standardized among clinical centers, and request to colonoscopy may vary at the discretion of referral physicians, which may cause a selection bias.…”

Bile Acid Sequestrants for Hypercholesterolemia Treatment Using Sustainable Biopolymers: Recent Advances and Future Perspectives

“…The BASs are also proven to be efficacious in the treatment of chronic diarrhea due to the malabsorption of BAs/BSs, often termed as bile acid diarrhea (BAD). − Studies had shown that patients with post-ileocecal resection experience a reduction in stool frequency and had an improvement in consistency of stool on a specific dose of cholestyramine per day; additionally, the urgency of defecation, perianal soreness, and flatus were also decreased in most cases. In patients with mild diarrhea, bile acid sequestrants provide symptomatic relief by lowering the concentration of free bile acids in the colon. ,− Figure represents the list of off label use of BASs reported in various literature and research guidelines.…”