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

Fan Wu, Yan Wang, Zhenpeng Mai, Zhichao Xu, Shenghui Li, Yu Li, Ruiqiao Yin, Jiamin Li, Zhenlong Yu, Yuzhuo Wu, Xiangge Tian, Xiaoying Feng, Xiaokui Huo (), Chao Wang () and Xiaochi Ma ()
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Fan Wu: Dalian Medical University
Yan Wang: Dalian Medical University
Zhenpeng Mai: Dalian Medical University
Zhichao Xu: Northeast Forestry University
Shenghui Li: Puensum Genetech Institute
Yu Li: Dalian Medical University
Ruiqiao Yin: Dalian Medical University
Jiamin Li: Dalian Medical University
Zhenlong Yu: Dalian Medical University
Yuzhuo Wu: Dalian Medical University
Xiangge Tian: Dalian Medical University
Xiaoying Feng: Dalian Medical University
Xiaokui Huo: Dalian Medical University
Chao Wang: Dalian Medical University
Xiaochi Ma: Dalian Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-64914-w

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