The Gut Microbiome-Estrogen Axis in Menopause: Implications for Body Composition, Cardiometabolic Health and...

Background/Objectives: Menopause is associated with profound endocrine, metabolic, immune, and microbial changes that may contribute to accelerated biological aging and increased cardiometabolic risk. The gut microbiome represents a potential interface between estrogen biology, host metabolism, inflammation, and systemic organ function. This narrative review examines the role of menopause-associated gut microbiome remodeling in microbiome-mediated metabolic aging, focusing on the estrobolome, microbial metabolites, organ crosstalk, and microbiome-targeted interventions. Methods: Relevant literature was identified through searches of PubMed/MEDLINE, Scopus, and Web of Science, supplemented by reference-list screening. Human observational and clinical studies, mechanistic investigations, systematic reviews, meta-analyses, and relevant guidelines were critically evaluated and synthesized narratively. No formal meta-analysis was performed. Results: Menopause-associated changes in gut microbial composition and function may influence estrogen metabolism through the estrobolome and modify the production of short-chain fatty acids, lipopolysaccharides, trimethylamine N-oxide, and bile acid metabolites. These pathways may contribute to chronic low-grade inflammation, insulin resistance, endothelial dysfunction, dyslipidemia, hepatic metabolic dysfunction, adipose tissue inflammation, adverse changes in body composition, sarcopenia, neuroinflammation, and urogenital microbial instability. Dietary patterns, fermentable fiber, physical activity, probiotics, synbiotics, phytoestrogens, and menopausal hormone therapy may influence components of this network, although the strength of evidence remains variable. Current data do not support the use of microbiome characteristics to select or dose hormone therapy. Conclusions: The gut microbiome may act as a dynamic mediator linking estrogen decline with metabolic and systemic aging after menopause. However, causality, individual variability, and clinical translation remain insufficiently established. Longitudinal studies integrating shotgun metagenomics, metabolomics, hormone measurements, standardized hormone therapy exposure, and clinical outcomes are needed to determine whether microbiome-derived biomarkers can support risk stratification and personalized interventions for healthier aging in postmenopausal women.