Revealing the adaptive metabolic differences of different sheep breeds in plateau areas based on the Gut-Cardiac axis.

Gut microbiota plays a significant role in maintaining the homeostasis of the gut internal environment, and the volatile fatty acids (VFAs) produced by it are the main source of energy utilization for the host. The cardiac, as a key metabolic organ of the body, its energy metabolism efficiency directly affects the body's tolerance to the hypoxic environment at high altitudes. To reveal the dynamic regulatory relationship between the rumen and the cardiac of Hu sheep during their response to the high-cold and hypoxic environment. This study conducted transcriptome sequencing on the cardiac tissues from both sheep breeds, and carried out interaction analysis of the differentially expressed genes (DEGs) with rumen microbiota, VFAs, and metabolites. The results showed that: A total of 616 DEGs (P<0.05) were identified in the cardiac of sheep of different breeds, among which 437 genes were up-regulated and 179 genes were down-regulated. By comparing with known transcription factors, it was found that genes highly expressed in Hu sheep, such as ATP2A3, NPPB, PDE3A, SLC25A4, and AKT3, were significantly enriched in the cGMP-PKG signaling pathway. In the study of the interaction between rumen microbial genera and cardiac-related DEGs, it was found that microbial genera such as Candidatus Saccharimonas and Succiniclasticum had a close positive correlation (P<0.05) with genes related to cardiac energy metabolism. Analysis of the interaction between genes and VFAs showed that acetic acid, propionic acid, butyric acid, and valeric acid play roles in regulating gene expression. WGCNA revealed that different metabolite modules were concentrated and enriched in Metabolic pathways, participating in cardiac energy metabolism. Metabolites such as Arachidonate, Adenine, and 6-Keto-prostaglandin F1alpha, together with SLC25A4 and AKT3, are involved in regulating cardiac energy metabolism. This study revealed that Hu sheep may regulate cardiac metabolism through rumen microbes and metabolites to cope with high-altitude hypoxic stress, providing a certain reference for understanding the response of Hu sheep to the high-altitude hypoxic environment.