Estrogen–gut microbiome axis: Physiological and clinical implications

Abstract

Low levels of gonadal circulating estrogen observed in post-menopausal women can adversely impact a diverse range of physiological factors, with clinical implications for brain cognition, gut health, the female reproductive tract and other aspects of women's health. One of the principal regulators of circulating estrogens is the gut microbiome. This review aims to shed light on the role of the gut microbiota in estrogen-modulated disease. The gut microbiota regulates estrogens through secretion of β-glucuronidase, an enzyme that deconjugates estrogens into their active forms. When this process is impaired through dysbiosis of gut microbiota, characterized by lower microbial diversity, the decrease in deconjugation results in a reduction of circulating estrogens. The alteration in circulating estrogens may contribute to the development of conditions discussed herein: obesity, metabolic syndrome, cancer, endometrial hyperplasia, endometriosis, polycystic ovary syndrome, fertility, cardiovascular disease (CVD) and cognitive function. The bi-directional relationship between the metabolic profile (including estrogen levels) and gut microbiota in estrogen-driven disease will also be discussed. Promising therapeutic interventions manipulating the gut microbiome and the metabolic profile of estrogen-driven disease, such as bariatric surgery and metformin, will be detailed. Modulation of the microbiome composition subsequently impacts the metabolic profile, and vice versa, and has been shown to alleviate many of the estrogen-modulated disease states. Last, we highlight promising research interventions in the field, such as dietary therapeutics, and discuss areas that provide exciting unexplored topics of study.

Impact of sex hormones on immune function and multiple sclerosis development

“…Estrogen-like compounds may also promote proliferation and growth of certain types of bacteria. 133 On the other hand, estrogens are metabolized by microbes secreting b-glucuronidase, an enzyme that deconjugates estrogen, allowing the 'active' metabolite to enter the bloodstream and bind to estrogen receptors. 134 Treatment with pregnancy levels of estrogen induces changes in the composition and diversity of the gut microbiota, associated with protection against EAE.…”

Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy

“…Accordingly, the survival and migration of endometrial stromal cells (ESCs) outside the uterine cavity is the major cause for the development of endometriosis. Current therapeutic alternatives consist of various hormone treatments, such as GnRH-agonists (GnRH-a), aimed at increasing the apoptotic rate in eutopic and ectopic endometrial cells from women with endometriosis [4].…”

The Microbiome Mediates Environmental Effects on Aging

“…Japan leads the world in life expectancy. [57] Daidzein, a common soy isoflavone, can be converted to the metabolite equol, but only in the presence of certain gut bacteria. [53] Yet interpopulation variation in soy's health effects suggests that there may be more to the story.…”

“…[55] Biosocial analysis of aging in the perimenopause [56] suggests that this could result from differences in microbial populations, related to endogenous and possibly also exogenous (such as dietary phytoestrogen) estrogen levels, since the gut microbiome regulates circulating estrogen through secretion of the enzyme β-glucuronidase, which deconjugates estrogens into active forms. [57] Daidzein, a common soy isoflavone, can be converted to the metabolite equol, but only in the presence of certain gut bacteria. [58] Interestingly, estimates of the proportion of equol producers (those harboring appropriate bacteria to produce equol) range from 20-30% among US populations to 50-60% among Japanese middle-aged women.…”