Deciphering functional landscapes of rumen microbiota unveils the role of Prevotella bryantii in milk fat synthesis in goats

The rumen microbiome is critical for regulating milk synthesis in dairy livestock, yet the molecular mechanisms linking microbial functions to host lipid metabolism remain poorly understood. While host genetics and microbial composition have been studied, integrative analyses of the rumen-blood-mammary gland axis remain lacking. Here, we present the goat rumen microbial reference gene catalog and 5514 metagenome-assembled genomes (MAGs) from 160 multi-breed rumen samples. Integrating this resource with lactation data from 177 Saanen dairy goats, we identify Prevotella spp. as keystone taxa driving concurrent increases in milk yield and fat percentage. Functional and metabolomic profiling reveals that Prevotella bryantii B14 synthesizes nicotinate, which is converted to nicotinamide in circulation. Using in vitro and in vivo models, we demonstrate that nicotinamide activates the mTORC1 pathway in mammary epithelial cells via GPR109A, which upregulates transcription factors SREBP and PPAR-γ and the downstream lipogenic genes FASN, ACCα, and SCD1 to promote milk fat synthesis. In contrast, the relative deficiency of P. bryantii B14 and the associated reduction in nicotinamide levels in the rumen of poor lactating dairy goats may represent a significant contributor to impaired lactation performance. Additionally, the enhanced hydrogenotrophic methanogenesis activity may also adversely affect their lactation phenotype. Our study establishes a causal link between rumen microbial metabolism and mammary lipid synthesis mediated by nicotinamide-mTORC1 signaling and identifies Prevotella abundance as a biomarker for precision breeding. These findings advance the understanding of microbiome-host crosstalk in lactation and provide actionable strategies for enhancing dairy productivity through microbiota-targeted interventions.