title: Immunological Consequences of Intestinal Fungal Dysbiosis.
abstract: Compared to bacteria, the role of fungi within the intestinal microbiota is poorly understood. In this study we investigated whether the presence of a "healthy" fungal community in the gut is important for modulating immune function. Prolonged oral treatment of mice with antifungal drugs resulted in increased disease severity in acute and chronic models of colitis, and also exacerbated the development of allergic airway disease. Microbiota profiling revealed restructuring of fungal and bacterial communities. Specifically, representation of Candida spp. was reduced, while Aspergillus, Wallemia, and Epicoccum spp. were increased. Oral supplementation with a mixture of three fungi found to expand during antifungal treatment (Aspergillus amstelodami, Epicoccum nigrum, and Wallemia sebi) was sufficient to recapitulate the exacerbating effects of antifungal drugs on allergic airway disease. Taken together, these results indicate that disruption of commensal fungal populations can influence local and peripheral immune responses and enhance relevant disease states.
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and the Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Wheeler
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and the Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Limon
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and the Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Agnieszka S
authors.initials: AS
authors.lastname: Bar
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and the Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Leal
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and the Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gargus
authors.affiliation: Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Brown
authors.affiliation: Genomics Core, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Funari
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Hanlin L
authors.initials: HL
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Crother
authors.affiliation: Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Moshe
authors.initials: M
authors.lastname: Arditi
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and the Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Department of Pathology and Laboratory Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. Electronic address: david.underhill@csmc.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Underhill
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, and the Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Electronic address: ili2001@med.cornell.edu.
authors.forename: Iliyan D
authors.initials: ID
authors.lastname: Iliev
mesh_terms: D000666:Amphotericin B / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001483:Base Sequence; D003092:Colitis / Q000276:immunology / Q000382:microbiology; D019587:Dietary Supplements; D004342:Drug Hypersensitivity / Q000276:immunology / Q000382:microbiology; D064806:Dysbiosis / Q000139:chemically induced* / Q000276:immunology*; D015725:Fluconazole / Q000009:adverse effects / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole