Multi-Omics Analysis Reveals the Negative Effects of High-Concentrate Diets on the Colonic Epithelium of Dumont Lambs

Feeding HC diets has been found to induce metabolic dysregulation in the colon. However, the mechanisms by which changes in colonic flora and metabolites damage the colonic epithelium are poorly studied. Therefore, the present experiment used a multi-omics technique to investigate the mechanism of colonic injury induced by high-concentrate diets in lambs. Twelve male Dumont lambs were randomly split into two groups: a low-concentrate diet (LC = concentrate/forage = 30:70) group and a high-concentrate diet (HC = concentrate/forage = 70:30) group. The results showed that the HC group presented significantly increased lipopolysaccharide (LPS) concentrations in the colonic epithelium and significantly decreased serum total cholesterol (TC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels (<i>p</i> < 0.05), which led to cavities and inflammatory cell infiltration in the colonic epithelium. The HC group had significantly lower pH and less VFAs in colon contents, as well as a significantly increased abundance of bacteria of the genera <i>[Eubacterium]_coprostanoligenes_group</i>, <i>Rikenellaceae_RC9_gut_group</i>, <i>Treponema</i>, <i>Clostridia_UCG-014</i>, <i>Alistipes</i>, <i>Ruminococcus</i>, <i>Christensenellaceae_R-7_group</i>, <i>UCG-002</i>, <i>Bacteroidales_RF16_group</i> and <i>Lachnospiraceae_AC2044_group</i> compared to the LC diet group. These microorganisms significantly increased the level of metabolites of cholic acid, chenodeoxycholic acid, LysoPA (P-16:0/0:0), methapyrilene, and fusaric acid. A transcriptome analysis showed that cytokine–cytokine receptor interaction, glutathione metabolism, and the peroxisome signaling pathway were downregulated in the colon epithelium of the lambs fed the HC diet. Therefore, the HC diet caused epithelial inflammation and oxidative damage by affecting the interaction between the microbial flora of the colon and metabolites and the host epithelium, which eventually disrupted colon homeostasis and had a negative impact on sheep health.