Microbial indole-3-acetamide alleviates polycystic ovary syndrome through HIF-2α-ceramide signaling.

Intestinal Collinsella aerofaciens and its metabolite indole-3-acetamide are significantly reduced in women with PCOS, and IAM activates HIF-2α signaling to improve the condition.

• Why it matters: Understanding how gut microbiota influence adipose tissue dysfunction in PCOS could reveal new therapeutic targets for this common reproductive and metabolic disorder.
• What they did: The study identified decreased C. aerofaciens and IAM levels in PCOS patients, demonstrated that C. aerofaciens produces IAM via an IAM synthase, and showed that IAM activates HIF-2α signaling to promote ceramide degradation.
• The result: An engineered probiotic producing IAM alleviated PCOS symptoms in mice, suggesting IAM's potential as a treatment for PCOS by linking gut dysbiosis to adipose tissue dysfunction.