Figure 1.

Potential mechanisms by which gut microbiome may participate in regulating the host’s sex hormone levels. (A) the glucuronidation of sex hormones catalyzed by uridine diphosphate-glucuronosyltransferase 2B (UGT2B) in the liver increases the water solubility, which promotes the excretion of the glucuronidated compounds via urine or bile to the small intestine. Part of the conjugated sex hormones are de-conjugated by β-glucuronidase from the commensal gut bacteria. After deconjugation, the free sex hormone molecules are reabsorbed via the portal system. (B) Certain bacterial enzymes, such as 3α-HSD, 17β-HSD, 20α-HSD, 5α-reductase, and 1720 lyase, may participate in the biosynthesis of steroid hormones in the intestine, whereas further investigation is required. (C) Some bacteria are important for the maintenance of the protective function of the mucus. Destruction of the intestinal barrier may facilitate the passage of gut bacteria into the systemic circulation and elicit a chronic state of inflammation, which may impair testicular function, including the testosterone production by Leydig cells. (D) Some gut microbes are involved in the metabolism of neuroactive compounds or regulation of the gut-brain mediator secretion, which may influence the activity of the central nervous system via the gut–brain axis. Gut microbiome may thus influence endogenous production of sex hormones via the hypothalamic–pituitary–gonadal axis.