Gut dysbiosis-mediated elevated steroid biosynthesis promotes PCOS phenotype in postnatal androgen-treated goat models.
Although many animal models for studying PCOS have been generated, sheep and goat modelsare the most appropriate for examining the complexity of PCOS due to their resemblances tohuman reproductive development. While considerable research has shown gestational T26 induced sheep PCOS models, the postnatal induction of PCOS and their interactions with thegut have not been investigated. Consequently, in the current investigation, we developed apostnatal DHEA-treated goat PCOS model and discovered that the goat model replicates thePCOS-like phenotype in women. Analyses of the gut microbiota and mycobiota of goatstreated with DHEA compared to vehicle controls revealed a considerable rise in the bacterialgenera Romboutsia and the fungal genera Zygosaccharomyces and Wickerhamiella. In contrast,the bacterial genera Akkermansia and the fungal genera Penicillium were reduced. In addition,DHEA treatment upregulated metabolic pathways such as steroid biosynthesis and arachidonicacid metabolism. The correlation network between gut microbiota and serum and faecalmetabolites revealed a positive correlation between microbiota and steroid and primary bileacid biosynthesis via squalene and 3 beta cholestenol-3-one in DHEA-treated goats.Furthermore, DHEA-treated goat faecal transplantation in mice resulted in poly ovarian cysts,indicating that goat PCOS models are ideal for studying complex phenotypes of PCOS. Also,our studies imply that the composition of the gut's microbial population may determine PCOSphenotype.