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Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice

2021; American Association for the Advancement of Science; Volume: 371; Issue: 6534 Linguagem: Inglês

10.1126/science.abd0919

1095-9203

Umang Jain, Aaron Ver Heul, Shanshan Xiong, Martin Gregory, Elora G. Demers, Justin Kern, Chin‐Wen Lai, Brian D. Muegge, Derek A. G. Barisas, J. Steven Leal-Ekman, Parakkal Deepak, Matthew A. Ciorba, Ta‐Chiang Liu, Deborah A. Hogan, Philip Debbas, Jonathan Braun, Dermot McGovern, David M. Underhill, Thaddeus S. Stappenbeck,

Inflammatory Bowel Disease

Alterations of the mycobiota composition associated with Crohn's disease (CD) are challenging to link to defining elements of pathophysiology, such as poor injury repair. Using culture-dependent and -independent methods, we discovered that Debaryomyces hansenii preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. D. hansenii cultures from injured mice and inflamed CD tissues impaired colonic healing when introduced into injured conventionally raised or gnotobiotic mice. We reisolated D. hansenii from injured areas of these mice, fulfilling Koch's postulates. Mechanistically, D. hansenii impaired mucosal healing through the myeloid cell-specific type 1 interferon-CCL5 axis. Taken together, we have identified a fungus that inhabits inflamed CD tissue and can lead to dysregulated mucosal healing.