Altered metabolome and microbiome features provide clues in understanding irritable bowel syndrome and depression comorbidity

Lijuan Han, Ling Zhao, Yong Zhou, Chao Yang, Teng Xiong, Lin Lu, Yusheng Deng, Wen Luo, Yang Chen, Qinwei Qiu, Xiaoxiao Shang, Huang Li, Zongchao Mo, Huang Shaogang, Suiping Huang, Zhi Liu, Wei Yang, Lixiang Zhai, Ziwan Ning, Chengyuan LinTao Huang, Chungwah Cheng, Linda L.D. Zhong, Shuaicheng Li*, Zhaoxiang Bian*, Xiaodong Fang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Irritable bowel syndrome (IBS) is one of the functional gastrointestinal disorders 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 IBS-specific microbiota, metabolites, and their interactions remain poorly understood. To address this issue, we performed metabolomic and metagenomic profiling of stool and serum samples based on discovery (n = 330) and validation (n = 101) cohorts. Fecal metagenomic data showed moderate dysbiosis compared with other diseases, in contrast, serum metabolites showed significant differences with greater power to distinguish IBS patients from healthy controls. Specifically, 726 differentially abundant serum metabolites were identified, including a cluster of fatty acyl-CoAs enriched in IBS. We further identified 522 robust associations between differentially abundant gut bacteria and fecal metabolites, of which three species including Odoribacter splanchnicus, Escherichia coli, and Ruminococcus gnavus were strongly associated with the low abundance of dihydropteroic acid. Moreover, dysregulated tryptophan/serotonin metabolism was found to be correlated with the severity of IBS depression in both fecal and serum metabolomes, characterized by a shift in tryptophan metabolism towards kynurenine production. Collectively, our study revealed serum/fecal metabolome alterations and their relationship with gut microbiome, highlighted the massive alterations of serum metabolites, which empower to recognize IBS patients, suggested potential roles of metabolic dysregulation in IBS pathogenesis, and offered new clues to understand IBS depression comorbidity. Our study provided a valuable resource for future studies, and would facilitate potential clinical applications of IBS featured microbiota and/or metabolites.
Original languageEnglish
Article number16
Pages (from-to)983–996
Number of pages14
JournalISME Journal
Volume16
Issue number4
Early online date8 Nov 2021
DOIs
Publication statusPublished - Apr 2022

Scopus Subject Areas

  • Biochemistry, Genetics and Molecular Biology(all)

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