The Rumen Microbiome and Its Metabolome Together With the Host Transcriptome Act to Regulate the Cold Season Adaptation Mechanism of Grazing Tibetan Sheep

BackgroundTibetan sheep are important ruminants on the Qinghai-Tibet Plateau. They can maintain a normal life and reproduce in harsh environments under extreme cold and low oxygen. However, the molecular and metabolic mechanisms underlying the adaptability of Tibetan sheep during the cold season are still unclear. Hence, we conducted a comprehensive analysis of rumen epithelial morphology, epithelial transcriptomics, microbiology and metabolomics in a Tibetan sheep model to understand the interaction between the rumen host and microbiota and their metabolites and to explore the potential regulatory mechanism of Tibetan sheep adaptability to the cold season of the plateau. ResultsMorphological analysis showed that the ruminal muscle layer thickness and nipple width of Tibetan sheep increased significantly during the cold season ( P <0.05), and the thickness of the stratum corneum, stratum granulosa and stratum spinous of the rumen epithelium increased significantly ( P <0.05). Transcriptomics analysis showed that the differential genes were primarily enriched in the PPAR signaling pathway (ko03320), legionellosis (ko05134), phagosome (ko04145), arginine and proline metabolism (ko00330), and metabolism of xenobiotics by cytochrome P450 (ko00980). Unique differential metabolites were identified in cold season, such as cynaroside A, sanguisorbin B and tryptophyl-valine, which were mainly enriched in arachidonic acid metabolism, arachidonic acid metabolism and linolenic acid metabolism pathways, and had certain correlation with microorganisms. Integrated transcriptome-metabolome-microbiome analysis showed that epithelial gene- GSTM3 expression was upregulated in the metabolism of xenobiotics by the cytochrome P450 pathway during the cold season, leading to the downregulation of some harmful metabolites; TLR5 gene expression was upregulated and CD14 gene expression was downregulated in the legionellosis pathway during the cold season. A large number of metabolites, such as glucosidic acid and vitamin A, were produced in the steroid hormone biosynthesis and retinol metabolism pathways. ConclusionThis study comprehensively described the interaction mechanism between the rumen host and microbes and their metabolites in grazing Tibetan sheep during the cold season. Under the stimulation of the cold plateau environment, the morphological structure of the rumen epithelium of Tibetan sheep undergoes adaptive changes. Rumen epithelial genes, microbiota and metabolites act together in some key pathways related to cold season adaptation.