biostudies-literatureChiaro TRNational Institute of Allergy and Infectious DiseaseNSF CAREERT32 genetics trainingPackard Fellowships in Science and EngineeringKimmel Scholars AwardNIH Innovator AwardNational Heart, Lung, and Blood InstituteNIH New Innovator AwardEdward Mallinckrodt Jr. FoundationAmerican Cancer Society Researcheaaf9044https://www.ebi.ac.uk/biostudies/studies/S-EPMC5994919biostudies-literatureUnknown9(380)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.Science translational medicineA member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice.PMC5994919R21 AI109122DP2AT008746-01R00HL102228-05IOS-1253278GM007464DP2GM111099-01AI95375O'Connell RMRound JLGogokhia LZac Stephens WPetersen CKubinak JLCox JBell RChiaro TRDelgado JCVoth WBrown JTebo AEStillman DJSoto RfalseA member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice.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.2017-01-01T00:00:00Z2017 Mar2024-11-13T12:43:30.823Z2019-03-26T23:41:08ZS-EPMC59949192827515410.1126/scitranslmed.aaf9044