Menopause Alters Gut Microbiome and Increases Cardiometabolic Risk in Hispanic Women Original paper

What was studied?

The study explored how menopause affects the gut microbiome and estrobolome (the subset of gut bacteria involved in metabolizing sex hormones), and how these changes may relate to cardiometabolic risk factors. Using a large, well-characterized sample from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), researchers performed shotgun metagenomic sequencing on stool samples from about 2300 participants, including premenopausal women, postmenopausal women, and age-matched men. A subset also underwent serum metabolomics to assess sex hormone metabolites. The primary aims were to assess whether menopause alters gut microbiome diversity and composition, to identify specific microbial taxa and functions associated with menopausal status, and to investigate the relationship between these microbiome features, circulating sex hormone metabolites, and cardiometabolic risk profiles.

Who was studied?

Participants were drawn from the HCHS/SOL, a large, diverse cohort of Hispanic/Latino adults in the US. The analytic sample included 295 premenopausal women, 1,027 postmenopausal women, and 978 men (divided into groups age-matched to pre-and postmenopausal women). Exclusion criteria included cancer and insufficient sequencing data. Menopausal status was based on self-report and further refined to exclude women with surgical menopause, hormone therapy, or ambiguous menopausal status. Men were matched to women by age, BMI, Hispanic/Latino background, and nativity to control for confounders. Cardiometabolic risk factors and detailed demographic and lifestyle data were collected for all participants. Serum metabolomics data were available for a subset of 346 women.

Most important findings

Postmenopausal women exhibited lower gut microbiome diversity and a composition more similar to men than to premenopausal women, even after adjusting for age and confounders. Specific taxa enriched in postmenopausal women included Bacteroides sp. strain Ga6A1, Prevotella marshii, and Sutterella wadsworthensis, while Escherichia coli-Shigella spp., Oscillibacter sp., Akkermansia muciniphila, Clostridium lactatifermentans, Parabacteroides johnsonii, and Veillonella seminalis were depleted. Functionally, postmenopausal women had increased microbial sulfate transport systems and decreased abundance of β-glucuronidase, a key estrobolome enzyme, suggesting reduced microbial deconjugation of sex steroid hormones. Correlations between gut microbial features and serum progestin metabolites in postmenopausal women indicate active microbial participation in sex hormone retention. Menopause-related microbiome changes, especially the loss of beneficial species like C. lactatifermentans, were associated with adverse cardiometabolic profiles, including higher waist circumference, lower HDL, and higher blood pressure.

Key implications

The findings suggest that menopause-induced hormonal changes drive a shift in the gut microbiome toward a less diverse, more male-like composition, with reductions in both beneficial bacteria and estrobolome activity. These microbial shifts may reduce the potential for microbial reactivation of sex steroid hormones, potentially exacerbating the hormonal deficiency of menopause. The observed associations between menopause-related microbiome alterations and adverse cardiometabolic risk factors underscore the gut microbiome’s potential role in mediating increased metabolic risk after menopause. These results highlight the need for further research on microbiome-targeted interventions or hormone therapies to mitigate postmenopausal metabolic risk and suggest that microbiome signatures could be useful biomarkers for menopausal status and related health risks.