Chronic diarrhea, bile acids, and Clostridia

Abstract

Excessive fecal bile acid (BA) loss causes symptoms in a large proportion of people diagnosed with irritable bowel syndrome with diarrhea, a common functional bowel disorder. This bile acid diarrhea (BAD) results from increased hepatic synthesis of BAs, with impaired negative feedback regulation by the ileal hormone fibroblast growth factor 19 (FGF19). In this issue of the JCI, Zhao et al. investigated BA metabolism, including fecal BAs, serum BAs and FGF19, in patients and controls. They identified associations with fecal bacterial BA metabolism and specific microbiota, especially Clostridium scindens. These findings have been tested in a mouse model using microbiota transplants and antibiotic treatment. This group of organisms has potential as a biomarker for BAD and to be a target for therapy.

The Role of Bile Acids in Chronic Diarrhea

“…Indeed, whereas patients with IBS-D have a higher proportion of Escherichia coli and decreased Clostridium leptum and Bifidobacterium (40), a recent report showed that 24.5% of patients with IBS-D exhibited excessive excretion of total BAs and increase in Clostridia bacteria (e.g., C. scindens), which was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4) (41). The latter finding suggested that Clostridia bacteria have potential as a biomarker for BAD and as a target for therapy (42), although this still requires formal testing in humans.…”

Dietary fiber-based regulation of bile salt hydrolase activity in the gut microbiota and its relevance to human disease

“…For example, patients whose main biological disturbance is robust deconjugation of primary bile acids may benefit from a BSH inhibitor 40 or cholylsarcosine, 41 whereas those patients who do not convert primary to secondary bile acids may benefit from bile acid binding resins like cholestyramine or targeted engraftment of Clostridia species. 42 Indeed, our findings provide evidence for the potential value of the gut microbiome and its co-metabolites as a prognostic platform for precision nutrition and other therapeutic strategies in patients with SBS. Such a paradigm may have relevance to other diseases such as intestinal motility disorders associated with SIBO and environmental enteric dysfunction where alterations in the small intestinal microbiota have been described.…”

Rol de los ácidos biliares en la diarrea crónica funcional y en el síndrome de intestino irritable con diarrea. Una revisión de la literatura

“…En un estudio en el que se realizó el análisis metagenómico y metabolómico en 290 pacientes con SII-D y 89 voluntarios sanos, se observó que el incremento de clostridiales se asoció positivamente con los niveles de AB en heces y 7αC4 sérico, con disminución de los niveles de FGF19 60 . El rol de los clostridiales en la disminución de la transformación de AB y su importancia en la patogénesis del SII-D necesita ser replicado, pero abre una puerta al tratamiento antibiótico en estos pacientes 61 .…”