Microbiome and metabolome features in inflammatory bowel disease via multi-omics integration analyses across cohorts

Lijun Ning, Yi-Lu Zhou, Han Sun, Youwei Zhang, Chaoqin Shen, Zhenhua Wang, Baoqin Xuan, Ying Zhao, Yanru Ma, Yuqing Yan, Tianying Tong, Xiaowen Huang, Muni Hu, Xiaoqiang Zhu, Jinmei Ding, Yue Zhang, Zhe Cui, Jing-Yuan Fang, Haoyan Chen () and Jie Hong ()
Additional contact information
Lijun Ning: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Yi-Lu Zhou: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Han Sun: Xuzhou Central Hospital, Clinical School of Xuzhou Medical University
Youwei Zhang: Xuzhou Central Hospital, Clinical School of Xuzhou Medical University
Chaoqin Shen: Zhongshan Hospital, Fudan University
Zhenhua Wang: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Baoqin Xuan: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Ying Zhao: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Yanru Ma: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Yuqing Yan: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Tianying Tong: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Xiaowen Huang: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Muni Hu: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Xiaoqiang Zhu: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Jinmei Ding: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Yue Zhang: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Zhe Cui: Renji Hospital, Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Jing-Yuan Fang: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Haoyan Chen: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road
Jie Hong: Shanghai Jiao Tong University School of Medicine. 145 Middle Shandong Road

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract The perturbations of the gut microbiota and metabolites are closely associated with the progression of inflammatory bowel disease (IBD). However, inconsistent findings across studies impede a comprehensive understanding of their roles in IBD and their potential as reliable diagnostic biomarkers. To address this challenge, here we comprehensively analyze 9 metagenomic and 4 metabolomics cohorts of IBD from different populations. Through cross-cohort integrative analysis (CCIA), we identify a consistent characteristic of commensal gut microbiota. Especially, three bacteria, namely Asaccharobacter celatus, Gemmiger formicilis, and Erysipelatoclostridium ramosum, which are rarely reported in IBD. Metagenomic functional analysis reveals that essential gene of Two-component system pathway, linked to fecal calprotectin, are implicated in IBD. Metabolomics analysis shows 36 identified metabolites with significant differences, while the roles of these metabolites in IBD are still unknown. To further elucidate the relationship between gut microbiota and metabolites, we construct multi-omics biological correlation (MOBC) maps, which highlights gut microbial biotransformation deficiencies and significant alterations in aminoacyl-tRNA synthetases. Finally, we identify multi-omics biomarkers for IBD diagnosis, validated across multiple global cohorts (AUROC values ranging from 0.92 to 0.98). Our results offer valuable insights and a significant resource for developing mechanistic hypotheses on host-microbiome interactions in IBD.

Date: 2023
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DOI: 10.1038/s41467-023-42788-0

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