Microbial Hydroxysteroid Dehydrogenases: From Alpha to Omega

Abstract

Bile acids (BAs) and glucocorticoids are steroid hormones derived from cholesterol that are important signaling molecules in humans and other vertebrates. Hydroxysteroid dehydrogenases (HSDHs) are encoded both by the host and by their resident gut microbiota, and they reversibly convert steroid hydroxyl groups to keto groups. Pairs of HSDHs can reversibly epimerize steroids from α-hydroxy conformations to β-hydroxy, or β-hydroxy to ω-hydroxy in the case of ω-muricholic acid. These reactions often result in products with drastically different physicochemical properties than their precursors, which can result in steroids being activators or inhibitors of host receptors, can affect solubility in fecal water, and can modulate toxicity. Microbial HSDHs modulate sterols associated with diseases such as colorectal cancer, liver cancer, prostate cancer, and polycystic ovary syndrome. Although the role of microbial HSDHs is not yet fully elucidated, they may have therapeutic potential as steroid pool modulators or druggable targets in the future. In this review, we explore metabolism of BAs and glucocorticoids with a focus on biotransformation by microbial HSDHs.

Degradation of Bile Acids by Soil and Water Bacteria

“…Bile acids, or bile salts in their de-protonated state, are surface-active steroid compounds that serve many functions in the digestive tract of vertebrates [ 1 , 2 ] and as regulatory signaling compounds [ 3 ]. These functions and the interplay of bile acids with gastrointestinal bacteria [ 4 , 5 , 6 , 7 , 8 , 9 , 10 ] are described in the accompanying review articles of this special issue. The focus of this review is on the current knowledge about the metabolic pathways of soil and water bacteria, which use bile acids as a carbon and energy source under aerobic and anaerobic conditions and their ecological and biotechnological implications.…”

Grand Challenge in Adrenal Endocrinology: Is the Legacy of the Past a Challenge for the Future of Precision Medicine?

“…For example, some recent data point to the possible role of gut microbioma in modulating cortisol metabolism, due to the presence of 11b-hydroxysteroid dehydrogenase activity that plays a pivotal role in glucocorticoid metabolism. As new 11-hydroxysteroid dehydrogenase microbial 11b-hydroxysteroid dehydrogenase enzymes are continually being discovered, a new mechanistic study of their impacts in disease models could be developed (70). Likewise, the role of aberrant G-protein coupled hormone receptors (GPCR) in the pathogenesis of adrenal tumors has been investigated for many years.…”

Role of Gut Microbiota in Bile-Acid Metabolism

“…Bacteria such as Ruminococcus gravus, Ruminococcus productus, Collinsella aerofaciens, and Clostridium absonum have the HSDH gene but have not been studied in detail. Although the luminal concentrations of these bile-acid metabolites in the large intestine are low, recent reports have reported anti-inflammatory, anti-bacterial, and wound healing promoting effects of these metabolites [14]; thus, further studies are required.…”