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

Umang Jain, Aaron M. Ver Heul, Shanshan Xiong, Martin H. Gregory, Elora G. Demers, Justin T. 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 P.B. McGovern, David M. Underhill, Thaddeus S. Stappenbeck

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1154-1159
Number of pages6
JournalScience
Volume371
Issue number6534
DOIs
StatePublished - Mar 12 2021

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