Spotlight on the Gut Microbiome in Menopause: Current Insights

Abstract

The gut microbiome is an important contributor to human health, shaped by many endogenous and exogenous factors. The gut microbiome displays sexual dimorphism, suggesting influence of sex hormones, and also has been shown to change with aging. Yet, little is known regarding the influence of menopause - a pivotal event of reproductive aging in women - on the gut microbiome. Here, we summarize what is known regarding the interrelationships of female sex hormones and the gut microbiome, and review the available literature on menopause, female sex hormones, and the gut microbiome in humans. Taken together, research suggests that menopause is associated with lower gut microbiome diversity and a shift toward greater similarity to the male gut microbiome, however more research is needed in large study populations to identify replicable patterns in taxa impacted by menopause. Many gaps in knowledge remain, including the role the gut microbiome may play in menopause-related disease risks, and whether menopausal hormone therapy modifies menopause-related change in the gut microbiome. Given the modifiable nature of the gut microbiome, better understanding of its role in menopause-related health will be critical to identify novel opportunities for improvement of peri- and post-menopausal health and well-being.

Keywords: estrobolome; estrogen; gut microbiome; menopause; microbial translocation; progesterone.

Figure 1

Enterohepatic recirculation of estrogens by the gut microbiome. Estrogens in the systemic circulation, produced by the ovaries, adrenal gland, and adipose or other tissues, undergo first-pass metabolism in the liver, and also may be conjugated with glucuronide or sulfate groups in the liver which facilitates biliary excretion. In the intestinal tract, conjugated estrogens are either excreted in feces, or deconjugated by gut microbiota with β-glucuronidase or sulfatase enzymes, termed the “estrobolome” – this allows estrogens to enter the enterohepatic circulation, and thus subsequently re-enter the systemic circulation and reach other tissues.

Figure 2

Summary of putative changes in the human gut microbiome related to menopause. (A) Trajectory of estradiol and progesterone concentration during a woman’s adulthood, showing declines during the menopausal transition and low levels post-menopause. (B) Diagram of putative gut microbiome and gut epithelium changes during menopause. With declining estradiol and progesterone, diversity of the gut microbiome and estrobolome potential is reduced, and microbiome composition becomes more similar to men. Additionally, declines in estradiol and progesterone may lead to permeability of the gut barrier, allowing microbial translocation to occur.