Research ArticleMICROBIOTA

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

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Science Translational Medicine  08 Mar 2017:
Vol. 9, Issue 380, eaaf9044
DOI: 10.1126/scitranslmed.aaf9044

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Fungi and inflammatory bowel disease

Crohn’s disease is associated with an increase in antibodies against the yeast Saccharomyces cerevisiae, implicating a role for this fungus in inflammatory bowel disease. Chiaro et al. now demonstrate that increased colonization of the mouse gut with S. cerevisiae aggravated colitis by increasing purine metabolism, leading to greater damage of the gut epithelia. Treatment with the clinical drug allopurinol, which blocks the purine pathway, reversed this damage. The authors report a positive correlation between anti-yeast antibodies in human serum and increased purine metabolism. These results suggest that allopurinol could be used for treating Crohn’s disease associated with increased anti-yeast antibodies.

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.

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