SYSTEMATIC REVIEW article
Front. Cell. Infect. Microbiol.
Sec. Intestinal Microbiome
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1680840
This article is part of the Research TopicImpact of Gut Probiotic Metabolites on Human Metabolic DiseasesView all 14 articles
Effect of Probiotic-Derived Metabolites on Hormonal and Metabolic Profiles in Women with Polycystic Ovary Syndrome (PCOS): A Systematic Review and Meta-Analysis
Provisionally accepted
Maneesh Kumar Maddirevula1
Vinod Kumar Nelson1*Mohamed Soliman2Bader Khalid Alanazi2
Ahmed Hegazy2
Dr Habeeb Ali Baig2*
Amro M. Soliman3Mansour Alanazi2- 1Mahathi College of Pharmacy, Madanapalle, India
- 2Northern Border University Faculty of Medicine, Arar, Saudi Arabia
- 3Concordia University of Edmonton, Edmonton, Canada
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Background: Polycystic ovary syndrome (PCOS) is a common endocrine–metabolic disorder linked to insulin resistance and hyperandrogenism. Gut microbiota–derived metabolites, including short-chain fatty acids (SCFAs), indoles, and bile acids, influence endocrine and metabolic pathways. Yet, no systematic review has specifically examined metabolite-targeted interventions in PCOS. Objective: To assess the effects of probiotic-derived metabolite interventions on hormonal and metabolic outcomes in women with PCOS. Methods: Following PRISMA 2020 and a PROSPERO-registered protocol (CRD42025543210), we searched MEDLINE, Embase, Web of Science, Scopus, Cochrane CENTRAL, and two Chinese databases to May 2025 without language restrictions. Eligible studies were randomized or quasi-randomized controlled trials ≥8 weeks. Two reviewers independently screened, extracted data, and assessed risk of bias (RoB 2). Pooled analyses used random-effects models, and evidence certainty was appraised with GRADE. Results: Seventeen trials (n = 1,214 women) were included, testing synbiotics (6), probiotics (7), sodium butyrate (2), Akkermansia muciniphila (1), and an SCFA blend (1). Interventions significantly reduced total testosterone (MD −0.19 ng/mL, 95% CI −0.30 to −0.08), LH/FSH ratio (SMD −0.46; 95% CI −0.66 to −0.26), fasting insulin (MD −2.4 µIU/mL; 95% CI −3.9 to −0.9), and HOMA-IR (MD −0.49; 95% CI −0.78 to −0.19). HDL-C increased modestly (MD +3.2 mg/dL; 95% CI +0.7 to +5.6). Evidence certainty was moderate for insulin-related outcomes and low for sex-hormone outcomes. Conclusion: Targeting gut-derived metabolites, particularly with sodium butyrate and multi-strain synbiotics, improves hormonal and metabolic markers in PCOS. Larger multicenter RCTs with metabolomic confirmation are warranted to establish clinical translation.
Keywords: pcos, Probiotics, Postbiotics, short-chain fatty acids, Testosterone, Insulin Resistance
Received: 06 Aug 2025; Accepted: 15 Oct 2025.
Copyright: © 2025 Maddirevula, Nelson, Soliman, Alanazi, Hegazy, Baig, Soliman and Alanazi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Vinod Kumar Nelson, vinod.kumar457@gmail.com
Dr Habeeb Ali Baig, docbaig@yahoo.com
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