Gut microbiome in PCOS associates to serum metabolomics: a cross‑sectional study Original paper

What was studied?

This research investigated the relationship between gut microbiota composition and serum metabolites in women diagnosed with polycystic ovary syndrome (PCOS). By employing a cross-sectional study design, the researchers combined untargeted serum metabolomics and 16S rRNA gene sequencing to explore the microbial and metabolic profiles of PCOS patients compared to healthy controls. The primary aim was to understand whether specific gut microbiota shifts were associated with altered metabolic patterns in PCOS and whether these patterns might explain aspects of the syndrome’s pathophysiology, particularly around insulin resistance and mood disorders.

Who was studied?

The study involved 20 women with PCOS and 20 age-matched healthy controls from the Pixian area of Chengdu, China. All participants were carefully screened to exclude confounding variables such as recent use of antibiotics, probiotics, contraceptives, or hormone treatments. The PCOS group was diagnosed using the Rotterdam criteria, a widely accepted diagnostic standard. Clinical characteristics confirmed that PCOS patients showed higher BMI, elevated testosterone, LH, LH/FSH ratios, and fasting insulin levels compared to controls. Their quality of life scores, measured by the SF-36 questionnaire, were notably lower, suggesting a tangible psychosocial impact likely linked to both metabolic and microbial disturbances.

What were the most important findings?

This study revealed two core findings: a distinct gut microbiome signature and a correlated serum metabolite profile in PCOS patients. The gut microbiome of the PCOS group exhibited lower microbial diversity and a specific taxonomic shift marked by higher abundances of Escherichia-Shigella and Alistipes. Conversely, beneficial genera such as Roseburia and Prevotella were reduced. These shifts in microbial populations were significantly correlated with alterations in serum metabolites, especially within the glycerophospholipid metabolism and energy metabolism pathways.

Specifically, PCOS patients demonstrated elevated levels of lysophosphatidylcholine (LPC) variants, phosphatidylcholine (PC), ganglioside GA2, and 1-linoleoylglycerophosphocholine. Meanwhile, metabolites associated with energy metabolism — including citric acid and nicotinate beta-d-ribonucleotide — were significantly reduced. Correlation analyses highlighted that reduced Prevotella_9 was linked to lower levels of these beneficial metabolites and higher levels of the LPC family, suggesting a mechanistic connection between microbial dysbiosis and metabolic dysfunction.

These microbial-metabolite associations potentially contribute to two hallmark features of PCOS: insulin resistance and mood changes. For instance, higher Escherichia-Shigella and Alistipes levels have previously been linked to depression, while increased LPC concentrations are implicated in inflammation and cardiovascular risk, both common comorbidities in PCOS patients.

What are the greatest implications of this study?

This study underscores the potential of microbiome-metabolome interplay as both a diagnostic and therapeutic target for PCOS. The distinct microbial and metabolic profiles identified in this research offer clues about the biological mechanisms underlying PCOS, particularly the role of gut microbiota in modulating lipid metabolism, energy balance, insulin resistance, and mental health. The identification of Escherichia-Shigella and Alistipes as major microbial markers alongside metabolites like LPCs and citric acid opens pathways for non-invasive biomarkers, enabling earlier diagnosis and monitoring of disease progression.

More importantly, the findings pave the way for microbiome-targeted interventions such as targeted probiotics, dietary interventions, or even fecal microbiota transplantation (FMT) to correct dysbiosis, improve metabolic health, and potentially alleviate mood disorders in PCOS patients. Clinicians should consider the gut microbiome as a central component in the metabolic and psychological management of PCOS, especially in cases where standard endocrine treatments provide incomplete relief.