Multiomics Reveals Alterations in the Gut Microbiome, Host Proteins, and Host Metabolites Correlating with SADS-CoV Pathogenicity and the Immune Response in Piglets

SADS-CoV, a coronavirus, is known to induce swine acute diarrhea syndrome. To explore the differences and commonalities in the pathogenesis mechanisms between highly pathogenic and low-pathogenic strains of SADS-CoV, we conducted an integrated analysis comprising proteomics, metabolomics, and short-chain fatty acid (SCFA) analysis, along with 16S rRNA sequencing of intestinal mucosa and fecal samples from piglets infected with SADS-CoV P7 (highly pathogenic)or SADS-CoV P83༈low-pathogenic༉. Additionally, we examined molecular events linked to potential pathogenicity and host immune responses subsequent to correlational analysis of diverse omics data. In the SADS-CoV P7-infected group, the abundance of unidentified members of the family Enterobacteriaceae was markedly greater than in either the control group or the SADS-CoV P83-infected group in the ileum mucosa and feces. The concentration of SCFAs was significantly lower in SADS-CoV P7-infected pigs than in SADS-CoV P83-infected pigs, and SCFA levels were negatively correlated with the abundance of Enterobacteriaceae and the abundance of the species Escherichia coli in the ileum mucosa. Compared to those in the SADS-CoV P83 group, the differentially expressed proteins in the SADS-CoV P7 group were predominantly linked to extracellular matrix (ECM)-receptor interactions and focal adhesion pathways. Following SADS-CoV P7 infection, there was an increase in both the adhesion force and the number of Escherichia coli O157 adherent to IPEC-J2 cells. Moreover, SADS-CoV P7 can modulate the adhesion of E. coli O157 to IPEC-J2 cells by regulating the expression of the ECM-related protein integrin alpha5 (ITGA5), suggesting that ITGA5 plays a pivotal role in the invasion of E. coli O157 into intestinal epithelial cells during SADS-CoV infection. A correlation exists among the multiomics profiles of the small intestinal mucosa and feces of piglets following infection with various generations of SADS-CoV. Understanding this correlation can help us better prevent the virus from harming piglets.