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Immune Response to Yeast & Increased Purine Metabolism May Exacerbate Crohn’s Disease

A new study reports that a strain of intestinal-dwelling yeast may exacerbate Crohn's disease, and blocking the fungus from causing problems in the gut could alleviate the symptoms of inflammatory bowel disorder in some patients. Approximately 1.6 million Americans currently live with inflammatory bowel disorders (IBD), and as many as 70,000 new cases are diagnosed every year. No cure exists for IBD, though many patients manage their symptoms with anti-inflammatory drugs. While several studies have illuminated links between intestinal bacteria and IBD, scant attention has been paid to the other types of microbes living in the gut, even though almost 70% of Crohn's disease patients are predisposed to mount immune reactions against yeast. In work that served as the cover story of the March 8, 2017 issue of Science Translational Medicine, Dr. Tyson Chiaro of the University of Utah School of Medicine and colleagues demonstrated that a strain of Saccharomyces cerevisiae aggravated intestinal damage in mouse models of colitis. The researchers determined that the yeast caused the rodents to produce elevated amounts of uric acid in their intestines. They gave yeast-colonized animals allopurinol (a clinical drug used to reduce uric acid), which reversed intestinal disease. To determine if yeast might cause similar effects in humans, the scientists examined serum from 168 healthy volunteers and observed a positive correlation between uric acid levels and circulating antibodies against S. cerevisiae. Testing Crohn’s disease patients for uric acid and immune responses to yeast could inform more targeted therapeutic interventions, the authors say. The open-access Science Translational Medicine article is titled “A Member of the Gut Mycobiota Modulates Host Purine Metabolism Exacerbating Colitis in Mice.”

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Online cover of March 8, 2017 issue of Science Translational Medicine. "Fungi Take Center Stage." A strain of yeast (yellow) that is part of the gut mycobiota exacerbates inflammatory bowel disease in a mouse model (Chiaro et al.). Yeast are shown in close proximity to the mouse gut epithelium (villi are represented by peaks and valleys) where they induce purine metabolism leading to production of uric acid (blue crystals), increased gut permeability, and consequently a worsening of colitis. Treating mice with the drug allopurinol, which reduces uric acid production, helps to ameliorate colitis in these animals. (Credit: Alexander Tokarev/Ella Maru Studio).

[Press release] [Science Translational Medicine article]