Multiomics reveals alterations in the gut microbiome, host proteins, and host metabolites correlating with SADS-CoV pathogenicity and the immune response in piglets

Xiaoyu Tang; Huang Chao; Chenyu Li; Jingshuai Sun; Wenjie Li; Yuan Sun; Tian Lan; Jingyun Ma

doi:10.1016/j.virs.2026.10.001

October 2026

Citation: Xiaoyu Tang, Huang Chao, Chenyu Li, Jingshuai Sun, Wenjie Li, Yuan Sun, Tian Lan, Jingyun Ma. Multiomics reveals alterations in the gut microbiome, host proteins, and host metabolites correlating with SADS-CoV pathogenicity and the immune response in piglets .VIROLOGICA SINICA, 2026, 41(5) : 1145-1164. http://dx.doi.org/10.1016/j.virs.2026.10.001

Multiomics reveals alterations in the gut microbiome, host proteins, and host metabolites correlating with SADS-CoV pathogenicity and the immune response in piglets

Xiaoyu Tang ^a,b,c ,
Huang Chao ^a,b ,
Chenyu Li ^a,b ,
Jingshuai Sun ^a,b ,
Wenjie Li ^a,b ,
Yuan Sun ^a,b ,
Tian Lan ^{a,b
,,} ,
Jingyun Ma ^{a,b
,,}

a. State Key Laboratory of Swine and Poultry Breeding Industry, South China Agricultural University, Guangzhou 510642, China;
b. Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, South China Agricultural University, Guangzhou 510642, China;
c. College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China

Corresponding author: Tian Lan, lantian2016@scau.edu.cn
Jingyun Ma, majy2400@scau.edu.cn
Received Date: 18 September 2025
Accepted Date: 01 October 2026
Available online: 06 October 2026

Abstract

Swine acute diarrhea syndrome coronavirus (SADS-CoV) infection causes severe acute diarrhea, vomiting, and lethality in piglets. To explore the molecular mechanisms by which intestinal flora regulate viral infection, we conducted multi-omics analysis [proteomics, metabolomics, short-chain fatty acids (SCFA) quantification] and 16S rRNA sequencing on intestinal mucosal and fecal samples from piglets infected with highly pathogenic SADS-CoV P7 stain or low-pathogenic SADS-CoV P83 strain. In both ileal mucosa and fecal samples, the abundance of Enterobacteriaceae was markedly higher in the highly pathogenic strain infection group than in either the control group or the low-pathogenic strain infection group. The concentration of SCFAs was significantly lower in the highly pathogenic SADS-CoV infected pigs than the low-pathogenic strain infected pigs, and SCFA levels were negatively correlated with the abundance of Enterobacteriaceae and Escherichia coli in the ileal mucosa. Compared with the low-pathogenic group, differentially expressed proteins in the highly pathogenic group were mainly associated with extracellular matrix-receptor interaction and focal adhesion pathways. SADS-CoV P7 infection increased both the adhesion capacity and the number of adherent Escherichia coli O157 on IPEC-J2 cells. This study demonstrates that the highly pathogenic SADS-CoV P7 strain remodels gut microbiota to exacerbate intestinal inflammation and tissue damage via activating integrin alpha5-mediated extracellular matrix-pathogen interactions. In contrast, the low-pathogenic SADS-CoV P83 strain exhibits attenuated virulence due to a lack of these regulatory pathways. This study elucidates the distinct pathogenic mechanisms of highly pathogenic and low-pathogenic SADS-CoV strains and provides critical insights for the development of broad-spectrum anti-coronavirus therapeutics and rational vaccine design.
- Swine acute diarrhea syndrome coronavirus (SADS-CoV)
- , Multiomics
- , Microorganisms
- , Escherichia coli (E. coli)

Electronic Supplementary Material

10.1016j.virs.2026.10.001-ESM3.xlsx
10.1016j.virs.2026.10.001-ESM2.xlsx
10.1016j.virs.2026.10.001-ESM4.xlsx
10.1016j.virs.2026.10.001-ESM1.docx

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