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Cell Host Microbe. 2019 Mar 13;25(3):377-388.e6. doi: 10.1016/j.chom.2019.01.007. Epub 2019 Mar 5.

Malassezia Is Associated with Crohn's Disease and Exacerbates Colitis in Mouse Models.

Author information

1
F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
2
Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
3
F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
4
Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.
5
F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA.
6
Department of Plant Pathology and Microbiology, University of California, Riverside, Riverside, CA 92521, USA.
7
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
8
F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: david.underhill@csmc.edu.

Abstract

Inflammatory bowel disease (IBD) is characterized by alterations in the intestinal microbiota and altered immune responses to gut microbiota. Evidence is accumulating that IBD is influenced by not only commensal bacteria but also commensal fungi. We characterized fungi directly associated with the intestinal mucosa in healthy people and Crohn's disease patients and identified fungi specifically abundant in patients. One of these, the common skin resident fungus Malassezia restricta, is also linked to the presence of an IBD-associated polymorphism in the gene for CARD9, a signaling adaptor important for anti-fungal defense. M. restricta elicits innate inflammatory responses largely through CARD9 and is recognized by Crohn's disease patient anti-fungal antibodies. This yeast elicits strong inflammatory cytokine production from innate cells harboring the IBD-linked polymorphism in CARD9 and exacerbates colitis via CARD9 in mouse models of disease. Collectively, these results suggest that targeting specific commensal fungi may be a therapeutic strategy for IBD.

KEYWORDS:

CARD9; Crohn disease; Malassezia; c-type lectin; mycobiome

Comment in

PMID:
30850233
PMCID:
PMC6417942
[Available on 2020-03-13]
DOI:
10.1016/j.chom.2019.01.007
[Indexed for MEDLINE]

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