Polycystic ovary syndrome (PCOS) is associated with dysfunctional ovulation, ovarian cysts and elevated androgen levels. The causes of PCOS are not fully understood and there is currently no aetiological cure.

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Previous human studies, with limited ethnic breadth, have shown that the composition of the gut microbiome in individuals with PCOS differs from that of individuals without the disease. Furthermore, PCOS often occurs with metabolic disorders, including insulin resistance and obesity, which are also characterized by gut microbial dysbiosis. Now, a new study from Yanli Pang, Changtao Jiang, Jie Qiao and colleagues provides insight on the mechanisms that link the gut microbiota to PCOS-associated ovarian and metabolic dysfunction.

“Exploring novel targets for therapeutic strategies is still a key challenge in PCOS research,” Jie Qiao points out. “In the lead up to this work we speculated that intestinal flora disturbance could be involved in the pathogenesis of PCOS.”

To test this hypothesis, the researchers analysed the gut microbiome composition, as well as metabolic function, of 43 healthy women and 50 women with PCOS. This analysis revealed that the composition of the microbiomes of participants in the PCOS group shared more similarities than the composition of the microbiomes from participants within the control group. Interestingly, Bacteroides vulgatus was notably increased in individuals with PCOS.

The scientists then transplanted the gut microbiota from study participants into mice. The microbiome transplants from women with PCOS resulted in insulin resistance and disrupted oestrous cycle and cyst-like follicles, thus mimicking the human symptoms. The administration of live B. vulgatus had similar effects on the mice as microbiome transplants from human participants with PCOS, indicating that B. vulgatus contributes to the pathogenesis of PCOS.

These data demonstrate that targeting the identified bile acid–IL-22 signalling axis presents a possible treatment strategy for patients with PCOS

The researchers also investigated the mechanisms that mediate the observed effects of B. vulgatus and report that B. vulgatus colonization alters bile acid metabolism, reducing certain species of bile acids that induce IL-22-secreting group 3 innate lymphoid cells (ILC3s) in the intestinal lamina propria. The number of ILC3s was reduced in mice transplanted with B. vulgatus, and IL-22 serum concentrations were decreased in both mice and humans with PCOS.

Insulin resistance, disrupted oestrous cycle and morphological changes to the ovaries in B. vulgatus-treated mice were rescued by supplementation with IL-22 or the bile acid glycodeoxycholic acid. These data demonstrate that targeting the identified bile acid–IL-22 signalling axis presents a possible treatment strategy for patients with PCOS.

The authors are now planning to build on this work. “We want to recruit more volunteers with PCOS to join the large-scale multicentre clinical trial to verify the effect of gut microbiota, bile acids or IL-22 on PCOS,” Jie Qiao concludes.