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

Author:

Jain Umang1ORCID,Ver Heul Aaron M.12ORCID,Xiong Shanshan1ORCID,Gregory Martin H.2ORCID,Demers Elora G.3ORCID,Kern Justin T.1,Lai Chin-Wen14ORCID,Muegge Brian D.125ORCID,Barisas Derek A. G.1ORCID,Leal-Ekman J. Steven1ORCID,Deepak Parakkal2ORCID,Ciorba Matthew A.2ORCID,Liu Ta-Chiang1ORCID,Hogan Deborah A.3ORCID,Debbas Philip6ORCID,Braun Jonathan6,McGovern Dermot P. B.67,Underhill David M.67ORCID,Stappenbeck Thaddeus S.18ORCID

Affiliation:

1. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

2. Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

3. Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.

4. Department of Inflammation and Oncology, Amgen Research, Amgen Inc., South San Francisco, CA 94080, USA.

5. Department of Medicine, VA Medical Center, St. Louis, MO 63106, USA.

6. F. Widjaja Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

7. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.

8. Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH 44195, USA.

Abstract

Fungal aggravation The gut microbiota includes not only prokaryotes, viruses, protists, and occasionally helminths, but also fungi. The role that fungi play in this symbiosis has long been overlooked. While investigating alterations to the gut microbiota in mice with mucosal damage and human subjects with Crohn's disease, Jain et al. discovered the fungus Debaryomyces hansenii localized to wounds in inflamed mucosal tissue (see the Perspective by Chiaro and Round). Impaired healing was associated with antibiotic treatment, overgrowth of the fungus, and subsequent induction of a type I interferon–CCL5 axis by macrophages. The fungus was observed within macrophages. Such persistent injury stimulus is a hallmark of inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. It is not known whether this salt-tolerant fungus is a natural symbiont, but it is used in the food industry for surface ripening of cheese and meat products. Science , this issue p. 1154 ; see also p. 1102

Funder

National Institutes of Health

Crohn’s and Colitis Foundation of America

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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