Fig 1.
Bile salt hydrolases act on circulating conjugated bile acids in the gut-liver axis.
(A) Bile acids synthesized in the liver and stored in the gall bladder enter the small intestine through the duodenum where they reach millimolar concentrations. The majority of bile acids (95%) are reabsorbed in the ileum and recirculate to the liver through the portal vein. The remaining population transit to the colon as they continue to be reabsorbed, and a small (<5%) amount exit through the feces. Recirculating bile acids access host tissues outside the intestines to impart systemic effects on host physiology. (B) BSHs cleave the amide bond in conjugated bile acids to open up the bile acid pool to increased complexity. The gut microbiota performs additional chemistry on deconjugated bile acids to generate the secondary bile acid pool, which can undergo enterohepatic circulation and be reconjugated in the liver. These transformations are illustrated to the right as conjugated CA is deconjugated, subjected to 7 α-dehydroxylation to become DCA, and subsequently reconjugated. (C) Monomeric BSH overlay from Bifidobacterium longum (PDB ID 2HEZ), Enteroccocus faecalis (PDB ID 4WL3), Lactobacillus salivarius (PDB ID 5HKE), and Clostridium perfringens (PDB ID 2BJF). Hydrolyzed TDCA in the CpBSH active site is coordinated by several loops that contain the most variation in the peptide backbone compared to the other structures. BSH, bile salt hydrolase; CA, cholic acid; CpBSH, C. perfringens BSH; DCA,; TDCA, taurodeoxycholic acid; PDB ID, Protein Data Bank ID.