(A) Cortisol is side-chain cleaved by DesAB and/or reversibly reduced/oxidized by NAD(H)-dependent 20α- and 20β-hydroxysteroid dehydrogenases (HSDHs), encoded by desC and desE, respectively. (B) Genomic structure of steroid-17,20-desmolase operon in gut microbes, C. scindens ATCC 35704 and B. desmolans ATCC 43058. (C) Metabolism of glucocorticoids by DesAB parallels the biochemistry of sugar transketolation. (D) Released in bile, allo-tetrahydrocortisol, but not tetrahydrocortisol, is a substrate for DesAB, forming 11β-hydroxyandrosterone, which can be further metabolized by other gut microbes belonging to the genus Eggerthella and Bacteroides by 17β-HSDH activity.