Menopause is the final stage of reproductive aging and is reached when women stop menstruating for twelve months. The menopause transition occurs over several years, during which a reduction in the number of ovarian follicles leads to a varied production of progesterone and estradiol, along with abnormal menstrual cycles that occur with or without ovulation. A characteristic event of the menopausal transition period is a decrease in ovarian hormones, which reduces negative feedback on the pituitary gland and results in a high synthesis of FSH. After menopause, peripheral tissues, such as adipose tissues, become the main producer of estrogen. Symptoms associated with the transition phase of menopause, such as vasomotor symptoms, mood and sleep changes, genitourinary symptoms including vaginal dryness and atrophy, as well as bone loss, vary among women.
Advances in next-generation sequencing technology have allowed researchers to study the microorganisms that colonize the body. Microbial cells exist in the human body in a ratio of approximately 1: 1 to human cells and play a significant role in human health and disease. The largest number of microbes are found in the digestive tract, which, taken together, form the gut microbiome. A healthy gut microbiome regulates the metabolism of food components and endogenous compounds. It can also trigger inflammation through the synthesis of bacterial lipopolysaccharides (LPS). Several studies have found that the gut microbiome affects the central nervous system. This bidirectional interaction, which exists across the gut microbiota-brain axis, affects metabolic, immune and neuroendocrine pathways.
The altered composition of the intestinal microbiome is now known to be associated with various diseases such as obesity, depression, diabetes, cardiovascular disease, colorectal cancer and inflammatory bowel diseases. The composition of the gut microbiome changes throughout life. The sexual dimorphism of the gut microbiome changes during puberty, post-puberty and flattens out when an individual reaches 40 years of age. Changes in the gut microbiome have also been observed after menopause. Previous studies have indicated similarities in the composition of the gut microbiome between postmenopausal women and men. However, a significant difference was found in gut microbial diversity between men and pre-menopausal women. After adjustment for obesity status and age, about ninety differentially abundant species were found among pre- and postmenopausal women.
On the contrary, there was a lower abundance of Faecalibacterium, Bulleidia and Firmicutes. A positive correlation was also found between estradiol and the intestinal flora of Gammaproteobacteria, in particular Shewanella putrefaciens and Erwinia amylovora. In postmenopausal women, higher levels of the sulfate transport system pathway and a lower incidence of the orthologue of the β-glucuronidase gene and pathogenic bacterial secretion pathways have been reported. Data on serum metabolomics indicate a reduction in intestinal species and functions in postmenopausal women. Postmenopausal depletion of microorganisms such as Akkermansia muciniphila was positively correlated with serum progestogen metabolites. A comparative study that analyzed the diversity of the gut microbiome in pre-and post-menopausal women with and without HIV virus revealed that post-menopausal women with HIV showed greater diversity of the gut microbiome.
The gut microbiome of postmenopausal women with HIV showed a higher level of Enterobacteria and a lower abundance of Prevotella copri. Alterations in the gut microbiome increase an individual’s susceptibility to many diseases. For example, a reduced abundance in Ruminococcus sp. and also of Faecalibacterium preusnitzii makes an individual vulnerable to Crohn’s disease. Several studies have also linked the abundance of Prevotella and Sutterella in the gut with obesity. Currently, research on menopause and the gut microbiome is still in its infancy. Although many studies have indicated the difference in gut microbiome composition between pre- and postmenopausal women, more research with larger study cohorts is needed to further establish this relationship. Additionally, limited research is available relating to the longitudinal composition within the person in the gut microbiome during the menopausal transition.
In the future, the mechanisms by which menopause could alter the composition of the gut microbiome will need to be investigated. In addition, it will be important to understand whether a decrease in estradiol and progesterone affects the gut microbiome, as progesterone suppresses the immune system and, consequently, makes an individual susceptible to various pathogenic diseases.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Peters BA et al. Internat J Women Health 2022; 14:1059-1072.
Yang M, Wen S et al. Dis Markers. 2022 Jul 25; 2022:3767373.
Singh V, Park YJ et al. Crit Rev Food Sci Nutr. 2022 May 30:1-16.
Dott. Gianfrancesco Cormaci
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