Journal Article

Human intestinal fungus Clavispora lusitaniae attenuates colitis through Pyruvate decarboxylase-derived Indole-3-ethanol

Wu, Fan, Li, Yu, Yu, Zhenlong, Tian, Xiangge, Xu, Zhichao, Wang, Yan, Mai, Zhenpeng, Yin, Ruiqiao, Huo, Xiaokui, Wang, Chao, Wu, Yuzhuo, Li, Jiamin, Feng, Xiaoying, Li, Shenghui, Ma, Xiaochi

2025

Overview

Gut mycobiome dysbiosis has been implicated in inflammatory bowel disease (IBD). However, it remains unknown whether specific fungal species identified by sequencing directly contribute to IBD pathogenesis. Here, based on analysis of three fecal metagenome datasets of IBD cohorts and a previously established cultivated gut fungi catalog, we identify an IBD-depleted intestinal fungus Clavispora lusitaniae strain P4013B. We show P4013B attenuates DSS-induced colitis in wild-type, antibiotics-treated, and germ-free mice through activation of aryl hydrocarbon receptor (AHR). Using an activity-guided isolation strategy, we identify the P4013B metabolite indole-3-ethanol (IEt) as the AHR agonist mediating the anti-colitis activity. We further validate the role of IEt via engineering strains that overexpress pyruvate decarboxylases producing high yields of IEt. Tea polysaccharide enhanced the anti-colitis activity of P4013B by promoting its proliferation and colonization in the colon. Together, these results suggest that C. lusitaniae P4013B may be explored as a potential probiotic for the treatment and prevention of IBD. Here, the authors show that a human gut fungus, Clavispora lusitaniae P4013B, alleviates colitis in mice through the activation of the aryl hydrocarbon receptor, in turn mediated by its metabolite indole-3ethanol, indicating its potential as a probiotic for inflammatory bowel disease.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13 / 13/1 / 13/31 / 13/51 / 38 / 38/77 / 38/91 / 631/326/193/2544 / 64 / 64/60 / 692/4020/1503/257 / 692/699/1503/257 / Animal models / Animals / Antibiotics / Aromatic compounds / Clavispora lusitaniae / Colitis / Colitis - chemically induced / Colitis - microbiology / Colon - microbiology / Colon - pathology / Colonoscopy / Datasets / Digestive system / Disease / Disease Models, Animal / Dysbacteriosis / Ethanol / Feces / Feces - microbiology / Female / Fungi / Gastrointestinal Microbiome / Gastrointestinal tract / Germfree / Gut microbiota / Humanities and Social Sciences / Humans / Hydrocarbons / Hypocreales - genetics / Hypocreales - metabolism / Indoles / Indoles - metabolism / Indoles - pharmacology / Inflammation / Inflammatory bowel disease / Inflammatory bowel diseases / Inflammatory Bowel Diseases - microbiology / Intestine / Kinases / Male / Mann-Whitney U test / Meta-analysis / Metabolites / Mice / Mice, Inbred C57BL / multidisciplinary / Multivariate analysis / Oral administration / Pathogenesis / Polysaccharides / Probiotics / Pyruvate decarboxylase / Pyruvic acid / Receptors / Receptors, Aryl Hydrocarbon - agonists / Receptors, Aryl Hydrocarbon - metabolism / Science / Science (multidisciplinary) / Taxonomy / Variance analysis