Differential Effects of Bile Acid Species in Intestine

Bile acids (BA) are produced in the liver from cholesterol to regulate several biological processes. A key site of BA signaling is the intestine, a tissue that secretes a multitude of peptide hormones that act on the pancreas, brain, and liver. At least two gut hormones are secreted in response to BAs: glucagon-like peptide-1 (Glp1), and fibroblast growth factor-19 (Fgf19). It’s unknown whether different BA species affect secretion of these hormones differently, or whether there are additional intracellular or secreted proteins targeted by BAs in intestine. The PI first demonstrated that different BA species have distinct effects on insulin sensitivity and lipid metabolism. In this work, she hypothesized that alterations in BA levels and composition affect gene expression and secretion of proteins in the intestine. She tested this hypothesis by determining the effects of BA levels and composition on intestinal gene expression using intestinal explants, oral gavage, and intestinal perfusion in mice, followed by tissue collection and transcriptional profiling. Moreover, she investigated the effects of BA levels and composition on the gut secretome using intestinal perfusion in mice, followed by mesenteric blood collection and proteomic analysis.