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7-alpha-hydroxysteroid dehydrogenase (7-alpha-HSDH), also known as cholanoate 7-alpha-dehydrogenase, is an oxidoreductase enzyme primarily localized within the human gut microbiota, including specific strains of Clostridium, Bacteroides, and Escherichia coli. It plays a pivotal role in the biotransformation of primary bile acids, such as cholic acid and chenodeoxycholic acid, by catalyzing the NAD(P)+-dependent oxidation of their 7-alpha-hydroxyl groups into 7-oxo intermediates. This enzymatic step is essential for the subsequent formation of secondary bile acids like ursodeoxycholic acid (UDCA), which serves as a vital signaling molecule and therapeutic agent. Industrially, 7-alpha-HSDH is highly valued as a biocatalyst for the commercial production of UDCA and its taurine conjugates used to treat gallstones and primary biliary cholangitis. Beyond synthesis, the enzyme is a target for microbiome-modulating therapies aimed at addressing metabolic disorders, irritable bowel syndrome, and liver injury, where bile acid pool composition is dysregulated. In clinical research, products of this enzyme's activity are also utilized as biomarkers to assess the pharmacodynamic effects of drugs targeting human steroid-modifying enzymes such as 11-beta-hydroxysteroid dehydrogenase type 1.
Biocatalytic biotransformation of primary bile acids into therapeutic secondary bile acids (e.g., UDCA) and modulation of the intestinal bile acid pool to regulate host farnesoid X receptor (FXR) and TGR5 signaling pathways.
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