A ubiquitous yeast strain may play a role in exacerbating inflammatory bowel disease (IBD), an animal study showed.
While research has shown that the composition of gut microbiota in people with IBD is different from that of healthy people, most of the attention has been focused on bacteria. The roles of other microorganisms, including yeasts, are still poorly understood.
In research published in Science Translational Medicine, Tyson Chiaro, of the University of Utah, Salt Lake City, and his colleagues inoculated sterile mice with either of two fungal species: Rhodotorula aurantiaca – an environmentally acquired yeast found in milk and fruit juices – or Saccharomyces cerevisiae – Baker’s yeast – for which some people with Crohn’s disease have been shown to have elevated antibodies. The mice were inoculated gradually over a period of a week to mimic consumption of food enriched with yeast products. The researchers then treated the mice with drugs to induce colitislike symptoms and analyzed colon tissues for damage. Mr. Chiaro and his colleagues found that colonization with S. cerevisiae, but not with R. aurantiaca, aggravated colitis and resulted in epithelial damage leading to greater gut permeability (Sci Transl Med. 2017;9[380] pii: eaaf9044]).
Mr. Chiaro and his colleagues then investigated whether heat-killed S. cerevisiae also induced aggravated colitis and found that it did not, suggesting that a metabolically active organism was required to aggravate disease. Mr. Chiaro and his colleagues performed screens of fecal metabolites in the mice and found that S. cerevisiae colonization enhanced purine metabolism, resulting in increased uric acid production.
To test whether this purine pathway was aggravating colitis, the researchers blocked it with allopurinol (10 mg/kg). The S. cerevisiae– inoculated mice that were treated with allopurinol had reduced uric acid–levels and ameliorated colitis–symptoms. The results suggest that allopurinol might be of more clinical value in treating IBD than previously thought. The drug has been used in patients with Crohn’s disease to increase the efficacy of other IBD medications, and “many patients who received adjunctive allopurinol therapy were reported to have major clinical improvement,” Mr. Chiaro and his colleagues noted. The results “suggest that some of the improvement might come from preventing yeast-induced–uric acid buildup in the intestine. Thus, allopurinol treatment in some IBD patients with adverse reactions to yeast and high uric acid might be of therapeutic benefit and should be explored.”
Mr. Chiaro’s coauthors reported a variety of individual grant and fellowship awards, including from the National Institute of Allergy and Infectious Disease and the National Institutes of Health. None declared commercial conflicts of interest.
