Differential rumen and hindgut microbiome and metabolome in Holstein female calves with divergent feed efficiency

BACKGROUND: Significant environmental problems have challenged animal agriculture, improving feed efficiency in animals has become a vital research direction for sustainable agriculture. Bacteria play a critical role in the feed efficiency of animals. However, our current understanding of bacteria communities in the gastrointestinal tract of high-feed efficiency animals and their metabolic mechanisms remains unclear. RESULTS: Twenty Holstein female calves were used in this multi-omics study that integrated metagenomic and metabolomic analyses of 20 Holstein female calves to investigate feed efficiency, as measured by residual feed intake (RFI). From an initial cohort of 84 calves, the 10 with the highest RFI (HRFI, low efficiency) and the 10 with the lowest RFI (LRFI, high efficiency) were selected at 84 days of age. Rumen fluid, feces, and serum samples from these calves were collected for subsequent analyses. We found that LRFI calves harbored rumen and fecal microbiomes with significantly different community structures and co-occurrence networks compared to HRFI calves. Multi-omics integration identified robust microbial and metabolite biomarkers discriminating RFI groups. These microbiomes were functionally linked to differential nutrient utilization, LRFI calves were characterized by enhanced starch and protein digestibility coupled with propionate-oriented fermentation, associated with key species like Erysipelotrichaceae_bacterium and Hungatella_sp. Conversely, HRFI calves showed higher fat digestibility and acetate production. Notably, serum glutamate was enriched in LRFI calves despite lower intake, correlating with potential microbial metabolites (ribitol, taurine). Subsequent validation confirmed that glutamate supplementation in mice improved nitrogen metabolism and gut barrier function. CONCLUSIONS: In summary, this multi-omics study reveals that high feed efficiency in calves is associated with distinct microbial ecosystems characterized by functions such as starch degradation and propionate production, where glutamate metabolism serves as a central node. Video Abstract.