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Debaryomyces is enriched in Crohn's disease intestinal tissue and impairs healing in mice.
- Source :
-
Science (New York, N.Y.) [Science] 2021 Mar 12; Vol. 371 (6534), pp. 1154-1159. - Publication Year :
- 2021
-
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.<br /> (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Amphotericin B pharmacology
Animals
Anti-Bacterial Agents pharmacology
Antifungal Agents pharmacology
Chemokine CCL5 metabolism
Colon microbiology
Colon pathology
Crohn Disease immunology
Debaryomyces growth & development
Female
Gastrointestinal Microbiome
Germ-Free Life
Humans
Ileum microbiology
Ileum pathology
Inflammation
Interferon Type I metabolism
Intestinal Mucosa immunology
Macrophages immunology
Macrophages microbiology
Male
Mice
Mice, Inbred C57BL
Crohn Disease microbiology
Crohn Disease pathology
Debaryomyces isolation & purification
Debaryomyces physiology
Intestinal Mucosa microbiology
Intestinal Mucosa pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 371
- Issue :
- 6534
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 33707263
- Full Text :
- https://doi.org/10.1126/science.abd0919