Polycystic Ovary Syndrome: Etiology, Current Management, and Future Therapeutics Original paper

What Was Reviewed?

This review presented a comprehensive analysis of the multifactorial causes, pathophysiology, and therapeutic approaches for polycystic ovary syndrome (PCOS). It placed particular emphasis on the role of gut microbiota dysbiosis and its systemic effects on insulin resistance, hyperandrogenism, and chronic inflammation. In addition to outlining traditional treatments, the paper critically evaluated emerging therapies such as probiotics, prebiotics, fecal microbiota transplantation (FMT), miRNA modulation, and IL-22 therapy. This review serves as a key resource for clinicians seeking a holistic understanding of PCOS, connecting microbiome research with endocrine and metabolic interventions.

Who Was Reviewed?

The review synthesized findings from a wide array of clinical studies, animal models, and experimental trials. It referenced data involving women of reproductive age diagnosed with various phenotypes of PCOS, including both obese and lean individuals. It incorporated rodent models, especially those induced by androgens or letrozole, to simulate PCOS pathology and examine microbiome manipulation outcomes. In its assessment of microbiota, the review drew from sequencing studies and intervention trials using specific probiotic strains such as Lactobacillus acidophilus, L. casei, Bifidobacterium bifidum, and prebiotics like inulin and resistant dextrin. These references grounded its recommendations in translational and mechanistic evidence.

What Were the Most Important Findings?

The review outlined several critical findings that directly connect gut microbiota dysbiosis with the clinical hallmarks of PCOS. A key mechanism involves increased gut permeability due to decreased populations of beneficial bacteria like Lactobacillus and Bifidobacterium, alongside an overgrowth of pro-inflammatory species such as Escherichia coli and Shigella. This dysbiosis allows lipopolysaccharides (LPS) to enter systemic circulation, stimulating immune responses that impair insulin receptor function and exacerbate insulin resistance. Hyperinsulinemia then stimulates androgen production by ovarian theca cells and reduces SHBG levels, increasing free testosterone and fueling PCOS symptoms.

The review also addressed microbial metabolites, particularly short-chain fatty acids (SCFAs) and bile acids. Women with PCOS showed reduced production of SCFAs like butyrate, which are vital for maintaining gut integrity and regulating inflammation. Moreover, altered bile acid profiles—especially reductions in glycodeoxycholic and tauroursodeoxycholic acid—were linked to disrupted hormonal balance and metabolic dysfunction. These major microbial associations (MMAs) illustrate how gut microbiota interact with ovarian steroidogenesis, glucose homeostasis, and the immune axis in PCOS.

Importantly, the review highlighted the therapeutic potential of microbiota restoration. Probiotic supplementation with specific strains led to improvements in insulin sensitivity, lipid profiles, and androgen levels. Prebiotics such as resistant dextrin demonstrated similar metabolic benefits. FMTs in animal models reversed hyperandrogenism and restored menstrual cycles, suggesting strong translational potential. Additionally, novel pathways involving IL-22 and miRNA regulation offer future targets for microbial and metabolic rebalancing in PCOS.

What Are the Implications of This Review?

This review has profound implications for the clinical management of PCOS. It reframes the condition as a microbiota-linked systemic disorder rather than solely an endocrine one. By mapping specific microbial patterns to the hallmarks of PCOS—including hyperandrogenism, insulin resistance, and anovulation—the authors offer a rationale for gut-targeted diagnostics and treatments. Clinicians may soon assess microbiome composition as part of a diagnostic workup, particularly in patients with metabolic dysfunction but unclear hormonal profiles.

Furthermore, the review validates a multi-pronged therapeutic strategy, integrating microbiota restoration with hormonal, metabolic, and reproductive targets. The demonstrated success of Lactobacillus and Bifidobacterium supplementation in improving PCOS biomarkers supports the clinical use of probiotics. Similarly, FMT, while currently limited to preclinical studies, presents a compelling intervention with the potential to reset dysregulated metabolic-hormonal loops. Lastly, novel therapies like IL-22 and miRNA modulation could personalize treatment, especially for patients with inflammatory or resistant phenotypes. Overall, this review builds a clear and actionable bridge between microbiome science and PCOS clinical care.