4.8 Article

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

Journal

SCIENCE
Volume 371, Issue 6534, Pages 1154-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abd0919

Keywords

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Funding

  1. Crohn's & Colitis Foundation
  2. Lawrence C. Pakula, MD IBD Innovation
  3. American College of Gastroenterology
  4. Career Development Award from the U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development Service [IK2 BX004909-01]
  5. NIH [NIH DK46763]
  6. NIH/VA [AT009741, AI127548, DK125296, IK2BX004909-01]

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The study revealed that Debaryomyces hansenii fungus inhabits incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD patients, impairing colonic healing. Mechanistically, D. hansenii affects mucosal healing through the myeloid cell-specific type 1 interferon-CCL5 axis.
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.

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