Gut microbiome dysbiosis in premature ovarian insufficiency and polycystic ovary syndrome: a prospective cohort observational study

Background Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are two major reproductive endocrine disorders associated with impaired ovarian function and infertility. Although gut microbiota dysbiosis has been implicated in both conditions, direct comparisons of their microbial and functional characteristics remain limited. Methods In this prospective cohort study, 102 women of reproductive age, including patients with PCOS and POI as well as healthy controls (NG), were recruited between March 2024 and March 2025. Gut microbial profiles were initially characterized by 16S rDNA amplicon sequencing in 101 fecal samples, and 90 fecal samples (30 per group) were subsequently subjected to metagenomics sequencing for comprehensive taxonomic and functional analyses. Differential taxa, microbial functions, and their associations with baseline characteristics were evaluated. Results Both PCOS and POI exhibited gut microbial dysbiosis characterized by reduced abundances of Bacteroides compared with healthy controls. Distinct disease-specific microbial signatures were identified. The PCOS microbiome was enriched in Escherichia coli , together with functional pathways associated with energy metabolism, lipopolysaccharide biosynthesis, biofilm formation, antimicrobial resistance, and environmental adaptation. In contrast, the POI microbiome was characterized by enrichment of Gemmiger , Subdoligranulum , and Clostridiales -related taxa, accompanied by enhanced aminoacyl-tRNA biosynthesis, fatty acid biosynthesis, glucuronate metabolism, and carbohydrate utilization pathways. Correlation analyses further demonstrated close associations between disease-specific microbial taxa, microbial functions, and host metabolic and reproductive hormone profiles. Conclusion PCOS and POI share common features of gut microbial dysbiosis but exhibit distinct taxonomic and functional signatures. These findings provide new insights into microbiome-associated mechanisms underlying female reproductive endocrine disorders.