Role of gut microbiota in the development of insulin resistance and the mechanism underlying polycystic ovary syndrome (PCOS) Original paper

What Was Reviewed?

This paper reviewed the role of gut microbiota in the development of insulin resistance (IR) and its contribution to the pathophysiology of polycystic ovary syndrome (PCOS). The authors synthesized a wide body of literature spanning clinical studies, animal models, and microbial metabolomics to illustrate how gut dysbiosis acts as a central mechanism driving PCOS through metabolic, inflammatory, and hormonal pathways. The review explored multiple axes of gut microbiota influence, including endotoxemia, short-chain fatty acid (SCFA) production, bile acid metabolism, branched-chain amino acid (BCAA) synthesis, the gut-brain axis, and hyperandrogenism. These interconnected pathways ultimately lead to IR, hyperinsulinemia, and hormonal imbalance, all of which underpin the key clinical features of PCOS, including ovulatory dysfunction, endometrial receptivity impairment, obesity, and metabolic syndrome.

Who Was Reviewed?

The review encompassed findings from both human and animal studies. Human studies included women diagnosed with PCOS compared to controls, covering lean, obese, insulin-resistant, and normo-insulinemic phenotypes. The authors also incorporated data from rodent models, particularly letrozole-induced PCOS rats and prenatal androgen exposure models, to investigate microbial composition shifts and their functional impact on reproductive and metabolic phenotypes. Specific microbial taxa were evaluated through 16S rRNA sequencing and metagenomics, while endocrine and metabolic parameters were tracked to map microbial influence on systemic physiology.

What Were the Most Important Findings?

The review identified major microbial associations (MMAs) that characterize PCOS-related dysbiosis. At the phylum level, PCOS patients demonstrated a decreased abundance of Bacteroidetes and increased Firmicutes, often resulting in a higher Firmicutes/Bacteroidetes ratio, which has been linked to obesity and metabolic syndrome. Reductions in Bifidobacterium, Lactobacillus, Faecalibacterium prausnitzii, and Roseburia were consistently reported. These microbial shifts compromise intestinal barrier function, leading to increased translocation of lipopolysaccharides (LPS), a key endotoxin that triggers chronic systemic inflammation via the TLR4-CD14 signaling pathway. This inflammation impairs insulin signaling and exacerbates hyperinsulinemia, which then stimulates ovarian androgen production and suppresses SHBG, intensifying the free androgen burden. Additionally, the review highlighted that BCAA-producing microbes such as Prevotella further aggravate insulin resistance. Bile acid metabolism was also altered, with decreased levels of beneficial bile acids like glycodeoxycholic acid and tauroursodeoxycholic acid. These changes interfere with signaling through FXR and GPBAR1, reducing insulin sensitivity.

What Are the Implications of This Review?

This review reframes PCOS as a condition deeply intertwined with microbiota-related metabolic and endocrine dysregulation. For clinicians, this connection offers actionable insights for diagnosis and treatment. The consistent microbial signatures associated with PCOS, such as reduced SCFA producers and increased LPS-producing gram-negative bacteria, support the potential for gut-targeted therapies. Dietary interventions that promote microbial diversity, particularly high-fiber, low-sugar regimens, may alleviate metabolic and reproductive symptoms. The paper also supports the use of probiotics (e.g., Lactobacillus and Bifidobacterium species), prebiotics (e.g., inulin), and fecal microbiota transplantation (FMT) as novel adjunct therapies. In animal studies, both probiotic and FMT interventions restored estrous cycles and improved ovarian morphology, suggesting that modulating the gut microbiome could directly impact ovulation and fertility. However, the authors emphasize that more randomized controlled trials and functional studies are necessary to validate these treatments and define phenotype-specific microbial targets.