Gut Bacteria Metabolize Natural and Synthetic Steroid Hormones via the Reductive OsrABC Pathway.

ABSTRACT: Steroid hormone metabolism by the gut microbiome affects host physiology, but the underlying microbial pathways remain incompletely understood. Here, we isolate a novel human gut bacterium, Clostridium steroidoreducens ^T strain HCS.1 that reduces cortisol and related steroid hormones to 3β,5β-tetrahydrosteroid products. Through transcriptomics and enzymatic discovery, we establish the C. steroidoreducens OsrABC steroid hormone pathway. OsrA is a 3-oxo-Δ¹-steroid hormone reductase that targets synthetic glucocorticoids, including prednisolone-a frontline Crohn's disease therapy. OsrB is a 3-oxo-Δ⁴-steroid reductase that converts steroid hormones to 5β-dihydrosteroid intermediates, which OsrC subsequently reduces to 3β,5β-tetrahydro products. Ho

SUBMITTER: Jacoby C 

PROVIDER: S-EPMC11482826 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature