The impact of estrogen status on the gut microbiome: a systematic review and meta-analysis

<h4>Background</h4>Estrogens have been proposed as modulators of gut microbiome (GM) composition, yet evidence from observational studies remains inconsistent.<h4>Objective</h4>This meta-analysis aimed to systematically summarise existing evidence on GM alterations in hypoestrogenic women - post-menopausal or premature ovarian insufficiency (POI) - compared to euestrogenic pre-menopausal controls.<h4>Methods</h4>PubMed, SCOPUS and Embase were searched through December 2024 for studies comparing GM characteristics between hypoestrogenic and pre-menopausal women. Primary outcome was α-diversity (Shannon index). Secondary outcomes included relative abundances of <i>Bacteroidetes</i>, <i>Firmicutes</i>, and the <i>Bacteroidetes</i> to <i>Firmicutes</i> ratio. Random-effects models were used for data synthesis.<h4>Results</h4>Out of 1092 studies screened, 7 met the inclusion criteria (n = 45 women with POI, n = 1222 post-menopausal women, n = 463 eustrogenic controls). No significant differences were observed in <i>α</i>-diversity (p=0.990), <i>Bacteroidetes</i> (p=0.440), or <i>Firmicutes</i> abundance (p=0.110) between hypoestrogenic and euestrogenic groups, irrespective of POI or postmenopause. Similarly, the <i>Bacteroidetes</i> to <i>Firmicutes</i> ratio showed no significant difference between the groups (p=0.400). Study heterogeneity was high (I² 61-99%).<h4>Conclusion</h4>Current evidence does not support consistent differences in GM diversity or major bacterial phyla between hypoestrogenic and euestrogenic women. Given the substantial heterogeneity, limited control of confounding factors, and variability in methodological quality, these findings should be interpreted with caution. High-quality, well-controlled studies are needed to better define the relationship between estrogen status and the GM.