Gut microbiome in PCOS associates to serum metabolomics Original paper

What Was Studied?

This cross-sectional study investigated the relationship between gut microbiota composition and serum metabolomic profiles in women with polycystic ovary syndrome (PCOS), using an integrative approach combining 16S rRNA gene sequencing with untargeted serum metabolomics. The researchers aimed to determine how specific microbial taxa in the gut correlate with alterations in circulating metabolites and whether these associations may help explain the metabolic and endocrine disturbances observed in PCOS. This integrative analysis focused on identifying major microbial associations (MMAs) linked with lipid metabolism, energy homeostasis, and inflammatory markers, shedding light on potential mechanisms underlying PCOS pathophysiology.

Who Was Studied?

The study enrolled 20 women with PCOS diagnosed using the Rotterdam criteria and 20 healthy controls from Chengdu, China. Participants were matched in age but differed significantly in body mass index (BMI), serum testosterone, luteinizing hormone (LH), LH/FSH ratio, and fasting insulin levels. All subjects provided blood and stool samples, and filled out SF-36 quality of life assessments. Strict exclusion criteria were applied to control for confounders such as recent antibiotic, probiotic, or hormonal therapy use, and all participants resided in the same geographical region to minimize environmental variability.

What Were the Most Important Findings?

Women with PCOS exhibited marked dysbiosis in their gut microbiota alongside distinct changes in serum metabolites. Microbial alpha diversity was significantly reduced in the PCOS group, and beta diversity analyses confirmed community-level differences. At the phylum level, PCOS patients showed increased Proteobacteria, Verrucomicrobia, and Fusobacteria, while Firmicutes, Bacteroidetes, and Actinobacteria were decreased. Genera such as Escherichia-Shigella, Alistipes, and Megamonas were enriched in PCOS, whereas beneficial taxa like Roseburia and Bifidobacterium were diminished.

Serum metabolomic analysis identified 15 significantly altered metabolites in the PCOS group. Elevated metabolites included various lysophosphatidylcholines, phosphatidylcholine (PC), ganglioside GA2, and 1-linoleoylglycerophosphocholine—all of which are associated with glycerophospholipid metabolism. Meanwhile, levels of nicotinate beta-d-ribonucleotide and citric acid, markers of nicotinamide and TCA cycle metabolism, respectively, were reduced, indicating impaired energy homeostasis and redox imbalance.

Correlation analyses showed that Prevotella_9 was positively associated with beneficial metabolites like citric acid and nicotinate beta-d-ribonucleotide, and negatively correlated with pro-inflammatory LPCs. Roseburia, a known butyrate producer, was negatively correlated with LPC (20:4). These MMAs suggest that reductions in SCFA-producing microbes and expansions of pro-inflammatory taxa contribute to insulin resistance, oxidative stress, and mood disturbances in PCOS.

What Are the Implications of This Study?

This study provides compelling evidence that PCOS is characterized by a dual disturbance: gut microbial dysbiosis and metabolic dysfunction, which are closely intertwined. Clinically, this suggests the potential for microbiota-informed diagnostics and therapeutic strategies in PCOS. The association of key taxa such as Roseburia and Escherichia-Shigella with specific metabolic pathways, including glycerophospholipid and TCA cycle metabolism, provides biological plausibility for microbial modulation of systemic insulin sensitivity and inflammation. Moreover, the co-occurrence of mental health symptoms and microbial shifts tied to indole and serotonin pathways suggests that the gut–brain–ovary axis should be further explored in PCOS.

From a therapeutic standpoint, restoring beneficial microbes and correcting lipid and energy metabolism through targeted probiotics, dietary modulation, or even bile acid-focused interventions may offer a new avenue for comprehensive PCOS management. Future studies using metagenomics, metatranscriptomics, and intervention trials are needed to validate the causality and clinical utility of these microbiome–metabolome signatures.