Considering the Relationship Between Menopause and the Aging of the Gut Microbiome
The composition of the gut microbiome changes with age in ways that contribute to loss of function and inflammation throughout the body. Evidence from animal studies suggests that the influence of the gut microbiome on long-term health may be similar to that of lifestyle choices such as exercise and diet. Here, researchers discuss what is known of the relationship between menopause and the gut microbiome. As is the case for immune aging, this is likely a bidirectional relationship, each side negatively impacting the other.
The oral and gut microbiota, constituting the largest ecosystem within the human body, are important for maintaining human health and notably contribute to the healthy aging of menopausal women. This paper presents the current understanding of the microbiome during menopause, with a particular focus on alterations in the oral and gut microbiota.
While sex hormones shape the gut microbiome, resulting in sexual differences in microbial composition, the gut microbiome also participates in regulating sex hormone levels, indicating a bidirectional relationship. Glucuronic acid conjugation marks estrogens for biliary excretion through urine and feces, and the removal of glucuronic acid releases estrogens to reabsorb into the circulation. Some gut bacteria, such as Clostridium, Bifidobacterium, and Lactobacillus, yield β-glucuronides and β-glucuronidases, which deconjugate or conjugate estrogens. These gene products from gut bacteria that metabolize estrogens are termed the estrobolome. The proportion of β-glucuronides and β-glucuronidases in the gut regulates the quantity of circulating estrogens. Some gut bacteria produce enzymes that can selectively deconjugate certain estrogens, thus changing the profile of circulating estrogens. In addition to estrogens, other sex hormones, including androgens and progesterone, are similarly metabolized by the gut microbiota.
Studies suggest a bidirectional interplay between the gut microbiome and sex hormones during menopause. Estrogens and progesterone act as substrates for several bacterial species and therefore may contribute to elevated gut microbial diversity; moreover, the increased diversity and deconjugation activity of certain bacteria help to recycle sex hormones. Without production from the ovary, the estrogen and progesterone levels remain low in postmenopausal women; hence, the recycling of sex hormones by the gut microbiome may become a significant source of circulating estrogens and progesterone.