The microbiota extends the reproductive lifespan by safeguarding the ovarian reserve

Abstract

Infertility is a devastating condition affecting one in six people globally. In many cases, the underlying causes are unknown. Emerging evidence suggests that the microbiota influences reproduction, yet the mechanistic link between the microbiota, ovarian function, and length of the fertile lifespan remain unexplored. Here we report that the microbiota controls the length of the reproductive lifespan by maintaining the primordial follicle pool, a process mediated by microbiota-derived short chain fatty acids modulating gene regulatory networks crucial for the survival of the ovarian reserve. Dietary perturbation of the microbiota during a critical developmental window is sufficient to diminish the ovarian reserve, reduce oocyte retrieval, and impair preimplantation embryo viability, mirroring challenges in human fertility treatments. Targeted interventions to restore microbiota improve assisted reproductive outcomes, particularly when implemented early. These findings reveal a novel contribution of host-microbe interactions in mammalian reproduction and demonstrate that the microbiota impacts ovarian function and fertility.