From Gut to Hormones: Unraveling the Role of Gut Microbiota in (Phyto)Estrogen Modulation in Health and Disease

The human gut microbiota regulates estrogen metabolism through the "estrobolome," the collection of bacterial genes that encode enzymes like beta-glucuronidases and beta-glucosidases. These enzymes deconjugate and reactivate estrogen, influencing circulating levels. The estrobolome mediates the enterohepatic circulation and bioavailability of estrogen. Alterations in gut microbiota composition and estrobolome function have been associated with estrogen-related diseases like breast cancer, enometrial cancer, and polycystic ovarian syndrome (PCOS). This is likely due to dysregulated estrogen signaling partly contributed by the microbial impacts on estrogen metabolism. Dietary phytoestrogens also undergo bacterial metabolism into active metabolites like equol, which binds estrogen receptors and exhibits higher estrogenic potency than its precursor daidzein. However, the ability to produce equol varies across populations, depending on the presence of specific gut microbes. Characterizing the estrobolome and equol-producing genes across populations can provide microbiome-based biomarkers. Further research is needed to investigate specific components of the estrobolome, phytoestrogen-microbiota interactions, and mechanisms linking dysbiosis to estrogen-related pathology. However, current evidence suggests that the gut microbiota is an integral regulator of estrogen status with clinical relevance to women's health and hormonal disorders. Estrogens are C-18 steroid hormones which are synthesized majorly by ovaries. Circulating estrogens undergo phase I oxidative hepatic metabolism, leading to the formation of catechol estrogens such as 16-OH and 2-OH. Estrogen metabolites then undergo conjugation before biliary excretion. The enteric bacterial genes (estrobolome) in the intestine deconjugates estrogen, influencing reabsorption. The factors like age, diet, antibiotics affect estrobolome, causing dysbiosis. The ratio of 2-OH to 16-OH metabolites indicates estrogen-cancer risk. image