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Sci Transl Med. 2017 Mar 8;9(380). pii: eaaf9044. doi: 10.1126/scitranslmed.aaf9044.

A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice.

Author information

1
Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
2
ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA.
3
Metabolomics Core, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
4
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
5
Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. june.round@path.utah.edu.

Abstract

The commensal microbiota has an important impact on host health, which is only beginning to be elucidated. Despite the presence of fungal, archaeal, and viral members, most studies have focused solely on the bacterial microbiota. Antibodies against the yeast Saccharomyces cerevisiae are found in some patients with Crohn's disease (CD), suggesting that the mycobiota may contribute to disease severity. We report that S. cerevisiae exacerbated intestinal disease in a mouse model of colitis and increased gut barrier permeability. Transcriptome analysis of colon tissue from germ-free mice inoculated with S. cerevisiae or another fungus, Rhodotorula aurantiaca, revealed that S. cerevisiae colonization affected the intestinal barrier and host metabolism. A fecal metabolomics screen of germ-free animals demonstrated that S. cerevisiae colonization enhanced host purine metabolism, leading to an increase in uric acid production. Treatment with uric acid alone worsened disease and increased gut permeability. Allopurinol, a clinical drug used to reduce uric acid, ameliorated colitis induced by S. cerevisiae in mice. In addition, we found a positive correlation between elevated uric acid and anti-yeast antibodies in human sera. Thus, yeast in the gut may be able to potentiate metabolite production that negatively affects the course of inflammatory bowel disease.

Comment in

PMID:
28275154
PMCID:
PMC5994919
DOI:
10.1126/scitranslmed.aaf9044
[Indexed for MEDLINE]
Free PMC Article

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