Figure 1.

Bile acids (BAs) in regulation of colonic epithelial Cl⁻ secretion. BAs are normally present in the colon at relatively low concentrations where they act via BA receptors, such as Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), to inhibit salt and water secretion into the lumen (left). We propose that such actions serve to promote normal colonic absorptive function. In some pathological conditions, increased delivery of BAs to the colon may result from either increased synthesis of primary BAs by hepatocytes or reduced ileal absorption. The resulting high levels of luminal BAs induce perturbations in the epithelial cell membranes to promote Cl⁻ secretion and inhibit Na⁺ absorption, thereby promoting luminal fluid accumulation (right). Such direct effects of BAs on the epithelium are amplified by indirect actions involving the release of neurotransmitters and mediators from the enteric nervous and mucosal immune systems (ENS and MIS, respectively). It is thought that, under such circumstances, increased colonic fluid secretion is a protective mechanism that serves to dilute the abnormally high levels of luminal BAs.