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

作者：Lijuan Han, Ling Zhao, Yong Zhou, Chao Yang, Teng Xiong, Lin Lü, Yusheng Deng, Wen Luo, Yang Chen, Qinwei Qiu, Xiaoxiao Shang, Li Huang, Zongchao Mo, Shaogang Huang, Suiping Huang, Zhi Liu, Wei Yang, Lixiang Zhai, Ziwan Ning, Chengyuan Lin, Tao Huang, Chung Wah Cheng, Linda L. D. Zhong, Shuaicheng Li, Zhaoxiang Bian, Xiaodong Fang · 发表于：The ISME Journal · 年份：2021 · DOI：10.1038/s41396-021-01123-5 · 被引用次数：123 · 研究领域：Gut microbiota and health、Diet and metabolism studies、Gastrointestinal motility and disorders

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 micro...