New data unraveling role of the gut microbiome in PCOS

Key takeaways:

• Overall biodiversity of the gut microbiome is decreased in polycystic ovary syndrome.
• Animal models suggest diet-independent factors are driving any changes.

BOSTON — Evidence suggests hyperandrogenism is associated with changes in the gut microbiome in women with polycystic ovary syndrome and the gut microbiome may play a causal role in PCOS metabolic dysregulation, according to a speaker.

“While the gut microbiome is quite variable in humans due to diet and geographical influences, meta-analyses of human studies revealed that women with PCOS have a consistent decrease in biodiversity of gut microbiota and changes in specific bacteria, including Bacteroides, that are associated with hyperandrogenism,” Varykina (Kina) Thackray, PhD, professor in the department of obstetrics, gynecology and reproductive sciences at the University of California, San Diego, and associate director of the UC San Diego Center for OB/GYN, told Healio before a presentation at ENDO 2024. “Our studies in mouse models of PCOS also indicate that these changes in the gut microbiome occur without any differences in diet, indicating that diet-independent factors are driving these changes. Altogether, these studies indicate that increased testosterone levels in women modulate the composition of gut microbiota and production of microbial metabolites, which can then influence the host and contribute to PCOS pathology.”

Thackray said antibiotic depletion of the gut microbiome in a PCOS-like mouse model showed that the gut microbiome was required for parameters of metabolic dysregulation associated with type 2 diabetes risk, such as abdominal adiposity and insulin resistance. “This is surprising because it indicates that the gut microbiome may be required for certain aspects of PCOS metabolic dysregulation and provides an opportunity to develop microbial-based therapies for PCOS,” Thackray told Healio.

Still, Thackray said much research is still needed to understand the complexity of host/microbe interactions in PCOS.

“While quite a few studies have shown changes in the gut microbiome in women with PCOS, we need to understand which changes in microbial species and metabolites are consistent in various populations and which ones are influenced by genetics and environmental factors,” Thackray told Healio. “We also need studies in animal models to determine the molecular mechanisms by which testosterone modulates host/microbe interactions in females via direct actions on gut microbes and indirect actions in host tissues such as the liver, gut and the immune system.”

Thackray also said preclinical studies are needed to identify next-generation microbial therapies to treat PCOS and clinical studies to determine the efficacy of pre-, pro- and postbiotics in treating various aspects of PCOS.