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

. doi: 10.1016/j.virs.2026.10.001

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

多组学解释仔猪肠道微生物组、宿主蛋白和宿主代谢物与SADS-CoV致病性和免疫应答相关的改变

唐晓钰 ^a,b,c ,
黄超 ^a,b ,
李辰雨 ^a,b ,
孙敬帅 ^a,b ,
李汶洁 ^a,b ,
孙媛 ^a,b ,
蓝天 ^a,b,, ,
马静云 ^a,b,,

a. 猪禽种业全国重点实验室, 华南农业大学, 广州, 中国;
b. 广东省农业动物基因组学雨分子育种重点实验室, 广州, 中国;
c. 华南农业大学动物医学院, 广州, 中国

通讯作者： 蓝天, lantian2016@scau.edu.cn; 马静云, majy2400@scau.edu.cn
收稿日期： 2025-09-18
录用日期： 2026-10-01

摘要

猪急性腹泻综合征冠状病毒(SADS-CoV)感染可导致仔猪出现严重急性腹泻、呕吐和致死性症状。为探索肠道菌群调控病毒感染的分子机制，我们对感染高致病性SADS-CoVP7毒株或低致病性SADS-CoV P83毒株的仔猪的肠黏膜和粪便样本进行了多组学分析(蛋白质组学、代谢组学、短链脂肪酸)和16SrRNA测序。在高致病性感染组中，回肠黏膜和粪便中肠杆菌科(Enterobacteriaceae)的丰度显著高于对照组和低致病性感染组。受高致病性病毒SADS-CoVP7感染猪的短链脂肪酸(SCFAs)浓度显著低于低致病性SADS-CoVP83感染猪，且SCFAs水平与回肠黏膜中肠杆菌科和大肠杆菌(Escherichia coli)的丰度呈负相关。与低致病性病毒感染组相比，高致病性病毒组的差异表达蛋白主要与细胞外基质-受体相互作用和黏着斑通路相关。高致病性病毒SADS-CoVP7感染后，大肠杆菌O157对IPEC-J2细胞的黏附力和黏附数量均增加。研究表明，高致病性SADS-CoVP7毒株通过重塑肠道菌群、激活整合素α5介导的细胞外基质-病原体相互作用，加剧肠道炎症和组织损伤。相比之下，低致病性SADS-CoVP83毒株可能由于缺乏这些调控途径而表现出减弱的毒力。本研究旨在阐明高致病性和低致病性SADS-CoV毒株的致病机制，为广谱抗冠状病毒药物和合理疫苗设计提供重要见解。
- 猪急性腹泻综合征冠状病毒
- , 多组学
- , 微生物
- , 大肠杆菌

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

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)

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