Gut microbiota and metabolic imbalance linked to pregnancy risks in PCOS

Gut microbiota and metabolic imbalance linked to pregnancy risks in PCOS | Image Credit: © Ekaterina - © Ekaterina - stock.adobe.com.

There are distinct gut microbiota and metabolic signatures associated with premature endometrial aging and adverse pregnancy outcomes in patients with polycystic ovary syndrome (PCOS), according to a study presented at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE).¹

Key microbial and metabolic differences identified

In PCOS patients, Parabacteroides merdae (P. merdae), a benefitial gut bacterium, was reduced, while branched-chain amino acids (BCAAs) were more prevalent. This may lead to worse endometrial function and adverse reproductive outcomes in this population.

“In clinical practice, we noticed that even younger women with PCOS who achieved pregnancy still faced unexpectedly high rates of miscarriage and other complications”, said Aixia Liu, MD, lead study author.

Systemic risks of PCOS

PCOS presents in up to 20% of reproductive-aged women worldwide and is a major driver of infertility. Fertility treatment reduces these risks, but the odds of complications such as gestational diabetes, miscarriage, and preterm birth are still higher in these patients. According to investigators, the factors behind this risk have remained unknown.

Symptoms of PCOS include hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology.² Increased rates of type 2 diabetes mellitus, gestational diabetes, cerebrovascular and cardiovascular events, endometrial cancer, and other adverse health outcomes have been reported in PCOS patients, highlighting the need for tailored treatment.

Comparing PCOS and non-PCOS cohorts

Across 44 cities in China, 220 women aged under 35 years were recruited for the trial.¹ Of these, 110 had PCOS and another 110 were matched controls. Investigators profiled differences between these cohorts through both gut microbiome sequencing and metabolomics.

Ageing and decidualization were evaluated through laboratory studies on endometrial stromal cells (ESCs). Overall, PCOS patients presented with significantly reduced microbial diversity. Investigators noted this population had less P. merdae, which has been linked to metabolic health.

BCAAs were also reported in serum metabolomics of patients with PCOS vs those without PCOS, with this trend especially pronounced for isoleucine. PCOS patients also presented with reduced levels of short-chain fatty acids.

Increased pregnancy risk and endometrial dysfunction

The odds of an adverse pregnancy outcome were increased 1.95-fold in the PCOS group vs the non-PCOS group. These included miscarriage, preterm birth, low birth weight, macrosomia, hypertensive disorders, gestational diabetes, and perinatal death.

Endometrial tissue also had increased isoleucine levels in PCOS patients. Additionally, investigators exposed ESCs to isoleucine in the lab and found increased markers of cellular senescence, alongside a weakened ability for decidualization.

Implications for early uterine aging and personalized interventions

According to Liu, this indicated ageing-like changes in the uterus far sooner than expected. Therefore, even women aged under 35 years may experience adverse impacts on endometrial health.

This data indicated possible efficacy of P. merdae and BCAAs as biomarkers for identifying patients with high-risk PCOS and providing personalized care. Liu recommended future research to assess the impact of dietary interventions, probiotics, and BAAA-restricted diets on these effects and pregnancy outcomes.

“The study provides compelling evidence that metabolic and microbial imbalances in PCOS are not only systemic but may directly impair endometrial receptivity, even in younger women,” said Anis Feki, MD, PhD, Chair-Elect of ESHRE.

References

1. Gut bacteria and amino acid imbalance linked to higher miscarriage risk in women with PCOS. European Society of Human Reproduction and Embryology. June 29, 2025. Accessed July 2, 2025. https://www.eurekalert.org/news-releases/1088637.
2. Azziz R, Carmina E, Chen Z, et al. Polycystic ovary syndrome. Nature Reviews Disease Primers. 2016. doi:10.1038/nrdp.2016.57