Integrated Multi-Omics Data Analysis Reveals Altered Metabolome Activity and Microbiome Composition in Irritable Bowel Syndrome

Abstract Background: Irritable bowel syndrome (IBS) is one of functional gastrointestinal disorders mainly characterized by chronic and/or recurrent symptoms of abdominal pain and irregular defecation. Changed gut microbiota has been proposed to mediate IBS; however, contradictory results exist, and the exact mechanism is still debatable. IBS-specific microbiota and metabolite remain poorly understand. To address this issue, we performed untargeted metabolomic and shotgun metagenomic profiling of stool and serum samples from discovery (n=330) and validation (n=101) cohorts of IBS and healthy individuals. Results: Fecal “omics” data show moderate dysbiosis compared with other disease, in contrast, serum metabolites show significant differences and have great power to discriminate IBS from healthy subjects. Specifically, 726 differentially abundant serum metabolites are identified, including fatty acyl-CoA enriched in IBS. Integrating microbiome and metabolome data, we identified 522 robust associations between differentially abundant species and fecal metabolites, of which three species are strongly associated with the low abundance of dihydropteroic acid. Moreover, the tryptophan enrichment correlates with the severity of IBS depression in both fecal and serum metabolomes. Conclusions: Collectively, our study unveils serum/fecal metabolome alterations and their relationship with gut microbiome and highlight the massive dysbiosis of serum metabolites which empower to discriminate IBS patients. Our study also provides a valuable resource for future studies to understand host-gut microbiota relationships, and facilitate potential clinical applications using microbiota and (or) metabolites to evaluate IBS patients with depression.