title: A member of the gut mycobiota modulates host purine metabolism exacerbating colitis in mice.
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 yeastSaccharomyces cerevisiaeare found in some patients with Crohn's disease (CD), suggesting that the mycobiota may contribute to disease severity. We report thatS. cerevisiaeexacerbated intestinal disease in a mouse model of colitis and increased gut barrier permeability. Transcriptome analysis of colon tissue from germ-free mice inoculated withS. cerevisiaeor another fungus,Rhodotorula aurantiaca, revealed thatS. cerevisiaecolonization affected the intestinal barrier and host metabolism. A fecal metabolomics screen of germ-free animals demonstrated thatS. cerevisiaecolonization 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 byS. cerevisiaein 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.
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Tyson R
authors.identifier: 0000-0002-8132-5186
authors.initials: TR
authors.lastname: Chiaro
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Ray
authors.initials: R
authors.lastname: Soto
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: W
authors.identifier: 0000-0002-8072-9023
authors.initials: W
authors.lastname: Zac Stephens
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Kubinak
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Charisse
authors.initials: C
authors.lastname: Petersen
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Lasha
authors.identifier: 0000-0003-3652-0377
authors.initials: L
authors.lastname: Gogokhia
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Rickesha
authors.identifier: 0000-0002-0554-0730
authors.initials: R
authors.lastname: Bell
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.|ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA.
authors.forename: Julio C
authors.identifier: 0000-0002-3455-1711
authors.initials: JC
authors.lastname: Delgado
authors.affiliation: Metabolomics Core, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.|Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: James
authors.identifier: 0000-0002-5977-2350
authors.initials: J
authors.lastname: Cox
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Warren
authors.identifier: 0000-0003-0632-6979
authors.initials: W
authors.lastname: Voth
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Jessica
authors.identifier: 0000-0002-3255-1486
authors.initials: J
authors.lastname: Brown
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: David J
authors.identifier: 0000-0002-5268-2416
authors.initials: DJ
authors.lastname: Stillman
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Connell
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.|ARUP Laboratories, 500 Chipeta Way, Salt Lake City, UT 84108, USA.
authors.forename: Anne E
authors.identifier: 0000-0001-9553-298X
authors.initials: AE
authors.lastname: Tebo
authors.affiliation: 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.
authors.forename: June L
authors.identifier: 0000-0002-7158-9874
authors.initials: JL
authors.lastname: Round
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D003092:Colitis / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D000069196:Gastrointestinal Microbiome; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology; D008297:Male; D008810:Mice, Inbred C57BL; D011687:Purines / Q000378:metabolism*; D012248:Rhodotorula; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000276:immunology; D013559:Symbiosis; D014527:Uric Acid / Q000097:blood
chemical_list: D000908:Antibodies, Fungal; D011687:Purines; D014527:Uric Acid