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: 1) observational / intervention studies, 2) assessing microbiome through 16S rRNA amplicon / 16S rRNA gene sequencing / metagenomics, 3) comparing microbiome between women with and without PCOS, 4) published from 2007 until 2025, and 5) articles available online. The exclusion criteria were: 1) language other than English or Spanish, 2) reviews, 3) abstracts/posters, 4) case reports, 5) full text not available, and 6) 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 A total of 159 studies were identified and screened for title, abstract, and full text. Eight studies met the criteria (2 rodent; 6 human studies). The quality assessment indicated that half of the studies (4/8) presented a high risk of bias. Regardless of the limited number of studies 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 today 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. 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. In this review, we systematically screen the current literature on the gut microbiome's association with mental health in women with PCOS and describe possible mechanisms. We did a comprehensive literature search across the PubMed database until July 2025. A total of 159 studies were identified and screened for title, abstract, and full text. Eight studies met the inclusion criteria (2 rodent; 6 human studies). The quality assessment showed that half of the studies presented a high risk of bias. Regardless of the limited number of studies and the low quality scores, all the studies indicated an association between the gut microbiome, PCOS, and mental health problems. The studies also consistently reported an increase in Gram-negative bacteria in women with PCOS and mental health issues. The review also describes the possible contributors in gut-brain-PCOS crosstalk, such as gut permeability, inflammation, short-chain fatty acids, neurotransmitters, gastrointestinal hormones, bile acids, and the sex hormone-gut microbiota axis. Our review highlights that the current state of the research on the Gut-Brain-PCOS axis is rather preliminary, and the existing studies possess various limitations and often lack rigorous study design. Therefore, 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.