Gut feelings–the gut microbiome as a regulator of mental health in polycystic ovary syndrome

Abstract

Importance: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive, metabolic, and mental health comorbidities. The exact mechanisms of PCOS-related psychological distress and the role of the microbiome in the process remain unclear. Objective: To systematically review the current literature on the gut microbiome’s association with mental health in women with PCOS and to review the possible mechanisms. Evidence Review: A comprehensive literature search across the PubMed database until July 2025. Studies were included if they met the following criteria: observational/intervention studies; assessing microbiome through 16S ribosomal ribonucleic acid amplicon/ 16S ribosomal ribonucleic acid gene sequencing/metagenomics; comparing microbiome between women with and without PCOS; published from 2007 until 2025, and articles available online. The exclusion criteria were: language other than English or Spanish; reviews; abstracts/posters; case reports; full text not available, and duplicates. Two independent reviewers screened all titles and abstracts to determine eligibility, and discrepancies were resolved through discussion. The methodological quality and the potential risk of bias were assessed following the Joanna Briggs Institute Critical Appraisal Checklist for Case–Control Studies. Findings: Atotal of 159 studies were identified and screened fortitle, abstract, and fulltext. Eightstudiesmetthe criteria (2 rodent, 6 human studies). The quality assessmentindicated that half ofthe studies(4/8) presented a highrisk of bias.Regardless ofthe limitednumber ofstudies and the low quality scores, all the studies highlighted the association of the gut microbiome in PCOS with mental health problems. Conclusions and relevance: Our review provides the first summary of the studies performed to date on the gut–brain axis in PCOS. Our review highlights that the current state of the research is rather preliminary, and the existing studies possess various limitations and often lack rigorous study design. Nevertheless, all the studies indicated an association between changes in gut microbiome and mental health indicators in PCOS. We also noted a consistent increase in Gram-negative bacteria in women with PCOS and mental health issues. More research is needed on humans with a bigger sample size, different ethnicities, and wider age groups to clarify the microbial patterns involved, and in parallel, the field should move from descriptive studies to mechanistic approaches. (Fertil Steril® 2025;124:931–47. ©2025 by American Society for Reproductive Medicine.)