Role of Microbiota-Derived Bile Acids in Enteric Infections

Abstract

In this issue of Cell, Alavi et al. report that infection by Vibrio cholerae is blocked by gut microbiome-mediated hydrolysis of bile acids. Cholera therefore joins amebic dysentery and Clostridioides difficile colitis as enteric infections profoundly influenced by the microbiome's impact on bile acid metabolism.

Figure.

Role of hepatically-synthesized primary and microbially-derived secondary bile acids in enteric infections. Primary bile acids cholate (CA) and chenodeoxycholate (CDCA) and are synthesized from cholesterol by hepatocytes. Primary bile acids can be further modified via conjugation with taurine or glycine within the liver (T(G)CA, T(G)CDCA). Once synthesized, primary bile acids enter into bile. Bile is stored in the gallbladder until release in the duodenum foil owing ingestion of a meal. Once within the GI tract, gut microbial enzymes convert host-derived conjugated primary bile acids into secondary bile acids. For example the primary bile acid taurocholate (TCA) is metabolized by the bile salt hydrolase (bsh) of Blautia obeum into cholate (CA). CA in turn is metabolized by Clostridium scindens 7α-dehydoxylation via the bai operon into deoxycholate (DCA). The primary bile acid TCA is essential for V. cholerae TcpP virulence activation and for germination of C. difficile spores. Conversion of TCA to CA by B. obeum BSH protects against cholera and C. difficile Conversion by C. scindens bai operon of the secondary bile acid CA to DCA increases granulocyte monocyte progenitors (GMPs) in the bone marrow to provide gut polymorphonuclear neutrophil (PMN) protection from the parasite Entamoeba histolytica.