Compositional and functional features of the female premenopausal and postmenopausal gut microbiota Original paper

What was studied?

This original research article investigated compositional and functional differences in the gut microbiota between premenopausal and postmenopausal women using a metagenome-wide association study (MWAS). Shotgun metagenomic sequencing of fecal samples enabled the authors to compare not only the taxonomic diversity and abundance of gut microbes but also the metabolic modules and biochemical pathways associated with the gut microbiome in each group. The study aimed to clarify how menopause and the associated decline in endogenous estrogen affect the gut microbiome and its potential implications for metabolic and immune health risks in postmenopausal women. The research also explored how specific microbial taxa and their metabolic activities might contribute to disease risk profiles characteristic of postmenopausal status.

Who was studied?

The study cohort comprised 24 premenopausal and 24 postmenopausal women, carefully matched for age and body mass index (BMI) to control for confounding variables. All postmenopausal individuals experienced natural menopause and had not used antibiotics for at least one month prior to sample collection. Additional exclusion criteria included a history of chronic or current infection, malignancy, or recent antibiotic use. Clinical data collected included bone mineral density (BMD), blood lipid profiles, lifestyle, diet, and exercise habits. No significant differences were observed between the groups in these clinical and lifestyle factors, ensuring that the observed microbiome differences could be attributed primarily to menopausal status.

Most important findings

Postmenopausal women exhibited significantly reduced gut microbiome richness and diversity at the gene, species, and genus levels, as measured by Shannon index and taxon counts. Taxonomic shifts included depletion of Firmicutes and Roseburia species and enrichment of Bacteroidetes and the toluene-producing genus Tolumonas in postmenopausal women. Functionally, the pentose phosphate pathway, a key source of cellular antioxidant capacity, was more prevalent in premenopausal women, while metabolic modules involved in homocysteine and cysteine biosynthesis, glycolysis, and amino acid degradation were enriched in postmenopausal women. Notably, Tolumonas negatively correlated with BMD, suggesting a potential link with osteoporosis risk. The study also highlighted that higher homocysteine biosynthesis in the postmenopausal gut microbiome may contribute to increased cardiovascular risk. These compositional and functional shifts suggest that menopause leads to a gut microbial environment less supportive of antioxidant defense and potentially more conducive to metabolic and immune dysfunction.

Key implications

The findings underscore menopause-associated gut microbiome alterations as potential contributors to increased risks of metabolic, cardiovascular, and bone diseases in postmenopausal women. Reduced microbial diversity and depletion of beneficial taxa such as Roseburia may compromise host metabolism and immune function, while enrichment of taxa and pathways linked to harmful metabolites (e.g., homocysteine, toluene) may exacerbate disease risk. These insights suggest that the gut microbiome represents a promising therapeutic target for interventions (e.g., specific probiotics, dietary modulation, or fecal microbiota transplantation) aimed at improving metabolic and immune health outcomes in postmenopausal women. Moreover, identified microbial and functional signatures may serve as valuable biomarkers for risk stratification or monitoring of menopause-related disease progression.