Project description: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 heart, 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 heart of Hu sheep during their response to the high-cold and hypoxic environment, this study conducted transcriptome sequencing on the hearts of Hu sheep and Tibetan sheep, and carried out interaction analysis of the differentially expressed genes with rumen microbiota, VFAs, and metabolites. The results showed that: A total of 616 differentially expressed genes (P＜0.05) were identified in the hearts 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 heart-related differentially expressed genes, 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; The interaction analysis between the differentially expressed genes and VFAs showed that acetic acid, propionic acid, butyric acid, and valeric acid participated in the regulation of gene expression in a positive and synergistic manner. WGCNA showed that different metabolite modules were concentrated and enriched in Metabolic pathways and participated in the process of cardiac energy metabolism. In addition, metabolites such as Arachidonate, Adenine, and 6-Keto-prostaglandin F1alpha had a positive regulatory relationship with SLC25A4 and AKT3 and were involved in cardiac energy metabolism. This study revealed that Hu sheep can conduct directional regulation of cardiac metabolism through rumen microbiota and metabolites to cope with the hypoxic stress at high altitudes, providing an important reference for a deeper understanding of the response mechanism of Hu sheep to the hypoxic environment at high altitudes.

Project description:Background: Hu sheep, renowned for their prolificacy and economic value, have been introduced to Xinjiang for intensive farming operations. However, their suboptimal adaptation to local harsh environments limits growth efficiency and health management. In contrast, Duolang sheep, an indigenous Xinjiang breed, exhibit exceptional environmental resilience, largely attributed to their unique rumen microbiome enriched with fiber-degrading bacteria, which enhance roughage utilization and stress tolerance. To address Hu sheep’s adaptive challenges, this study applies Ligilactobacillus salivarius KS1018, a probiotic strain isolated from Duolang sheep, to Hu sheep, investigating its role in improving rumen microbial homeostasis, metabolic adaptation, and physiological resilience under Xinjiang’s environmental conditions.Results: Thirty-two male Hu lambs were allocated into four groups: Control (C) and three treatment groups receiving daily doses of 0.5×109 CFU/d (low-dose group, LLS, 1.0×109 CFU/d (medium-dose group, MLS), or 1.5×109 CFU/d (high-dose group, HLS) for 56 days. Although growth performance did not reveal significant enhancement, supplementation with the high dose of L. salivarius KS1018 (HLS group) significantly reduced ruminal NH3-N (p < 0.05) and increased total VFAs (p = 0.043), alongside elevated serum triglycerides (p = 0.021) and β-hydroxybutyrate (p < 0.05), indicating enhanced nitrogen utilization and ketogenesis. Rumen metabolomics revealed dose-dependent metabolic shifts: group HLS prioritized oxidative phosphorylation and pyrimidine metabolism (p < 0.001), while group MLS upregulated branched-chain amino acid biosynthesis (p < 0.01). Procrustes analysis confirmed strong microbiome-metabolome coordination (M2 = 0.56, p = 0.001), linking Lachnospira and Negativicutes enrichment to VFA production and redox homeostasis. Group HLS exhibited a decline in ruminal pH, suggesting a potential risk of subacute acidosis at higher doses.Conclusions: L. salivarius KS1018 optimizes rumen metabolism through microbial-host crosstalk, improving nitrogen efficiency and stress resilience in Hu sheep. The strain promoted ketogenesis and oxidative phosphorylation pathways, which alleviated oxidative stress and enhanced immune function under environmental challenges. Notably, the arid-adaptive genetic traits likely contribute to stabilizing rumen microbial networks, mimicking the superior roughage utilization capacity of its native Duolang sheep host. Our findings highlight the potential of L. salivarius KS1018 as a metabolic modulator in ruminant nutrition, redefining its role beyond traditional growth-centric applications.

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