Multi-omics insights into key microorganisms and metabolites in Tibetan sheep's high-altitude adaptation.

Tibetan sheep gastrointestinal microbial communities and metabolites showed adaptive differences with altitude, but we do not know which flora or metabolites may play an important role in acclimatization to the altitude environment. Therefore, we systematically analyzed the microbial structure and metabolites in the rumen and feces of Tibetan sheep at two altitudes (4,424 m and 2,364 m) using amplicon sequencing and untargeted metabolomics. The results showed that the bacterial communities differed greatly between the two groups, with high altitude Tibetan sheep having a higher forage fermentation capacity, and the abundance of some bacteria and fungi that were conducive to the decomposition of cellulose in rumen fluid increased significantly (especially Bacteroidota, Neocallimastigomycota, and Ascomycota), and the short chain fatty acids and NH-N produced by metabolism also increased. There was also a significant increase in the abundance of Naganishia, which is prone to survive in extreme environments. In addition, the metabolite profiles in the rumen and feces of Tibetan sheep at two altitudes were also significantly different, and further correlation analysis showed that the differential bacteria in the rumen were mainly related to the products related to amino acid metabolism and lipid metabolism, and the differential bacteria in the feces were mainly correlated with some metabolites related to antibacterial, anti-inflammatory, anti-tumor and other disease treatment components. Collectively, these changes in microbiota and metabolites may have facilitated the adaptation of Tibetan sheep to the harsh plateau environment, contributing to their better survival and reproduction. This study provides a basis for research on the mechanisms of adaptation of Tibetan sheep to the plateau environment.