IBD Severity and Fungi in Microbiome

IBD Severity and Fungi in Microbiome
Source: Limon et al.1
The microbiome includes not just bacteria, but also fungi, viruses and parasites. While most of the attention has been on bacterial components of the microbiome, new research links a commensal yeast found on human skin to disease severity in inflammatory bowel disease (IBD).

Linking Common Fungi with IBD Severity

In a new paper published in Cell Host & Microbe, Limon et al. examined commensal fungi associated with both Crohn's disease patients and healthy controls and identified a fungal agent more abundant in disease patients which might exacerbate inflammatory bowel disease (IBD)1.

The researchers compared fungal abundance in the guts of healthy controls and Crohn's disease patients. Several fungal genera were associated with Crohn's disease; among them, increased presence of Malassezia spp. One in particular, M. restricta, was most strongly associated with patients carrying the Crohn's disease risk allele CARDS12N. CARD9 is involved in anti-fungal innate immunity. Malassezia spp. were rare in the healthy controls1.

Confirming IBD Association with Induced Colitis Models

“Our data suggest that changes in intestinal fungi and host responses to intestinal fungi may contribute to disease in a subset of patients with [Crohn's Disease]. The data suggest that intestinal colonization with M. restricta, a common commensal fungus found typically on the skin, may increase disease severity and that genetic factors, especially CARD9 polymorphisms, are important in defining the inflammatory response to colonization.”
–Limon et al.1

M. restricta is a commensal yeast commonly found on human skin. Limon et al. gavaged specific pathogen free (SPF) C57BL/6J mice with this fungus and then induced colitis with dextran sulfate sodium (DSS). Mice which received the fungus displayed more severe colitis compared to controls. In a subsequent set of experiments, the researchers used two better controlled systems:

  1. Germ-free C57BL/6NTac mice from Taconic were colonized with a minimal flora: Altered Schaedler Flora (ASF). The ASF B6 mice were then either maintained as controls or gavaged with M. restricta and treated with DSS.
  2. Germ-free C57BL/6NTac mice from Taconic Biosciences were either maintained as germ-free controls or colonized with M. restricta and then treated with DSS.
In both the ASF B6 and the germ-free B6, presence of M. restricta exacerbated DSS-induced colitis. This indicated the effect was directly induced by presence of M. restricta and not due to influence of the agent on other components of the microbiota1.

How M. restricta Exacerbates Inflammatory Response

Limon et al. performed further experiments to understand the mechanism of M. restricta's effect on colitis, concluding that "Together, the data suggest that M. restricta exacerbates colitis directly by stimulating inflammatory responses via CARD9". While the factors involved in Malassezia colonizing the gut of IBD patients are unclear, identification of Malassezia as a factor which worsens disease points to targeting of fungal agents as a potential new therapeutic angle1.

1. Limon, J. J.; Tang, J.; Li, D.; Wolf, A. J.; Michelsen, K. S.; Funari, V.; Gargus, M.; Nguyen, C.; Sharma, P.; Maymi, V. I.; Iliev, I. D.; Skalski, J. H.; Brown, J.; Landers, C.; Borneman, J.; Braun, J.; Targan, S. R.; Mcgovern, D. P.; Underhill, D. M. Cell Host & Microbe 2019, 25 (3).