Gut and vaginal microbiomes on steroids: implications for women's health

Abstract

This review discusses the interactions of steroids with the gut and vaginal microbiomes within each life phase of adult women and the implications for women's health. Each phase of a woman's life is characterized by distinct hormonal states which drive overall physiology of both host and commensal microbes. These host-microbiome interactions underlie disease pathology in disorders that affect women across their lifetime, including bacterial vaginosis, gestational diabetes, polycystic ovary syndrome (PCOS), anxiety, depression, and obesity. Although many associations between host health and microbiome composition are well defined, the mechanistic role of the microbiome in women's health outcomes is largely unknown. This review addresses potential mechanisms by which the microbiota influences women's health and highlights gaps in current knowledge.

Keywords: estrogens; gut microbiome; menopause; polycystic ovary syndrome; pregnancy; progestins.

Figure 1.. Women’s life phases are characterized by distinct changes in hormonal milieu and vaginal microbiota.

Estrogens and progesterone follow a cyclical pattern of release during the menstrual cycle (A), which influence the composition of the vaginal microbiota (VM), where Shannon index is a measure of diversity (B). Pregnancy (C) is characterized by a lack of hormonal cyclicity and steadily increasing sex steroids to maintain pregnancy. The initial change in hormone levels relative to the follicular phase (FP) alters the composition of the VM during pregnancy (D), which later returns to a state similar to that of the secretory phase of the menstrual cycle. Hormone levels return to pre-pregnancy values postpartum (PP). At menopause (E), ovarian function declines and sex steroid levels drop precipitously. The endocrine changes of menopause coincide with drastic changes to the VM (F), including a decrease in Lactobacillus relative abundance.

Figure 2.. Systemic effects and modulation of estrogens.

Estrogens have widespread effects throughout the body and are central to many aspects of women’s health. In addition to their central effects, estrogens act on, and are acted on, by the human microbiome. The GM consists of microbes that produce β-glucuronidase. This enzyme can deconjugate estrogens that were bound for excretion, causing them to reenter the body and remain active [7]. The VM composition is influenced by estrogens in the body via its effects on the vaginal epithelium [12]. Vaginal glycogen increases in response to estrogens and drives Lactobacillus spp. dominance in the VM [11].