Gut microbiota-derived short-chain fatty acids promote follicular maturation via gWAT-ovary axis in mammals

Previous studies have demonstrated that gut microbiota regulates reproductive performance in mammals. Our prior research identified the gut microbiota-ovary axis as an important contributor to the superior follicular development observed in Chinese indigenous Meishan sows, yet the underlying mechanisms remain unclear. This study aims to elucidate the mechanism through which gut microbiota regulates follicular development.

Fecal microbiota transplantation (FMT) from Meishan sows promoted follicular maturation in recipient Landrace × Yorkshire sows, evidenced by increased numbers of antral follicles, secondary follicles, and corpora lutea, accompanied by decreased atretic follicles. Additionally, FMT altered reproductive hormone profiles, significantly elevating estradiol secretion during the estrous cycle prior to sampling. Multi-omics analyses identified four key bacterial species of Fibrobacter intestinalis, Lactobacillus mucosae, Bifidobacterium thermophilum, and Ruminococcin flavefaciens, along with short-chain fatty acids (SCFAs), that are closely associated with follicular maturation. These microbial species and their shared metabolites SCFAs promoted follicular maturation and ovulation rate by inhibiting apoptosis of ovarian granulosa cells, thus reducing follicular atresia. Mechanistically, SCFAs activated G-protein-coupled receptor 43 (GPR43), which is highly expressed in peri-ovarian gonadal white adipose tissue (gWAT). This SCFAs-mediated activation of GPR43 stimulated leptin secretion from gWAT in a concentration-dependent manner, consequently suppressing granulosa cell apoptosis and promoting follicular maturation. Furthermore, in a large-scale validation trial, dietary SCFAs supplementation increased litter size by approximately 5.91%.

Collectively, gut microbiota-derived SCFAs promote follicular maturation and increase litter size in sows by stimulating leptin secretion from peri-ovarian gWAT, thus providing novel insights into enhancing reproductive outcomes in mammals. Video Abstract.