Fungal aggravation
The intestinal 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. When investigating changes in the intestinal microbiota in mice with mucosal damage and human individuals with Crohn’s disease, Jain et al. discovered the fungus Debaryomyces hansenii located on wounds in inflamed mucous tissue (see the Perspective of Chiaro and Round). Impaired healing was associated with treatment with antibiotics, overgrowth of the fungus and subsequent induction of an axis of interferon-CCL5 type I by macrophages. The fungus was observed inside macrophages. This 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 symbiote, but it is used in the food industry for the surface ripening of cheeses and meat products.
Science, this problem p. 1154; see also p. 1102
Summary
Changes in the composition of mycobiota 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 found that Debaryomyces hansenii preferably located in and was abundant in intestinal wounds of mice not fully healed and inflamed mucous tissues of human CD subjects. D. hansenii cultures of injured mice and inflamed CD tissues impaired colon healing when introduced into conventionally bred or gnotobiotic injured mice. We re-isolated D. hansenii wounded areas of these rats, fulfilling Koch’s postulates. Mechanically, D. hansenii impaired mucosal healing through the specific type 1 myeloid cell interferon-CCL5 axis. Together, we identified a fungus that inhabits the inflamed tissue of CD and can lead to unregulated healing of the mucosa.