The Multi-Omics Analysis Revealed a Metabolic Regulatory System of Cecum in Rabbit with Diarrhea

SIMPLE SUMMARY: In July 2020, China completely banned the addition of antibiotics to feed, which had a huge impact on animal husbandry, such as the increased incidence of some intestinal diseases. In this study, the pathogenesis of diarrhea in rabbits fed with antibiotic-free diet was studied by multi-omics analysis. The study found that the relative abundances of Firmicutes and Proteobacteria in the cecum of diarrhea-afflicted rabbits changed significantly. Most of the differential expression genes identified were related to cecum inflammation and immune response, and a total of 652 differential metabolites were identified, mainly involved in inflammation-related metabolic pathways such as bile secretion, folic acid resistance, and tryptophan metabolism. In addition, Fournierella was positively correlated with myricetin and ursolic acid; thus, it might further cause bile secretion and tryptophan metabolism disorders, aggravate intestinal inflammation, change intestinal permeability, reduce host immunity, and lead to diarrhea in rabbits. ABSTRACT: With the comprehensive prohibition of antibiotics in the feed industry in China, the incidence of diarrhea in rabbits increased, such as loss of appetite, vomiting, and excretion of atheromatous feces. In order to explore the pathological and the molecular mechanisms of the diarrhea in the rabbitry fed with antibiotic-free diet, we used microbial metagenomics, transcriptome, and non-targeted metabolomics sequencing. The results showed that the Firmicutes level was significantly decreased (p < 0.001) and the Proteobacteria level was significantly increased (p < 0.05). The functional enrichment of cecum revealed that most differentially expressed genes (DEGs) were expressed in immune, inflammatory, and metabolic processes. The enrichment of the cecal fecal metabolites focused on the bile secretion, antifolate resistance, and tryptophan metabolism pathways, which are mainly associated with inflammation. The results of correlation analysis showed that Fournierella was positively correlated with myricetin, ursolic acid, and furtherly might cause bile secretion and tryptophan metabolism disorder, aggravate intestinal inflammation, change intestinal permeability, and reduce host immunity, leading to diarrhea in rabbits. This study provides a theoretical basis for illustrating the reason for diarrhea and developing new feeds for the health of rabbits.