Little is known about the role of gut fungi in regulating a healthy gut microflora and in contributing to inflammatory disorders. Most studies of gut microflora focus on commensal bacteria which make up the majority of microbes in the gut. Numerous studies have documented effects of intestinal bacteria on tuning mucosal immunity and in instructing tissue development and repair. Antibiotic use, host genetics, and diet influence the bacterial microbiota and susceptibility to intestinal inflammatory disease. What about fungi? Our overall hypothesis is that intestinal fungal dysbiosis influences the immune system in ways that can increase susceptibility to inflammatory disease and that can be targeted to increase resistance to inflammatory disease. In this renewal proposal, we document that disruption of the ?normal? mycobiome in mice causes increased susceptibility to colitis and to allergic asthma. We propose studies aimed at understanding how antibiotic use, host genetics, and diet influence the intestinal fungal microbiota (?mycobiota?) in the near and long-term. We will characterize how common (Candida and Saccharomyces) and less well-known (Wallemia, Epicoccum) fungi influence susceptibility to intestinal inflammatory disease.

Public Health Relevance

Growing evidence suggests that fungi in the gut (the fungal microbiota, or ?mycobiome?) influence health and susceptibility to disease. We have previously observed that fungi and immune responses to fungi can influence severity of colitis in mouse models and in patients with inflammatory bowel disease. In this project we will characterize how antibiotic, genetic, and dietary perturbation of the mycobiome influence colitis and investigate how changes in gut fungal populations persist.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
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Perrin, Peter J
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Cedars-Sinai Medical Center
Los Angeles
United States
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Limon, Jose J; Skalski, Joseph H; Underhill, David M (2017) Commensal Fungi in Health and Disease. Cell Host Microbe 22:156-165
Paterson, Marissa J; Oh, Seeun; Underhill, David M (2017) Host-microbe interactions: commensal fungi in the gut. Curr Opin Microbiol 40:131-137
Wheeler, Matthew L; Limon, Jose J; Bar, Agnieszka S et al. (2016) Immunological Consequences of Intestinal Fungal Dysbiosis. Cell Host Microbe 19:865-73
Underhill, David M; Pearlman, Eric (2015) Immune Interactions with Pathogenic and Commensal Fungi: A Two-Way Street. Immunity 43:845-58
Tang, Jie; Iliev, Iliyan D; Brown, Jordan et al. (2015) Mycobiome: Approaches to analysis of intestinal fungi. J Immunol Methods 421:112-121
Underhill, David M; Iliev, Iliyan D (2014) The mycobiota: interactions between commensal fungi and the host immune system. Nat Rev Immunol 14:405-16
Iliev, Iliyan D; Underhill, David M (2013) Striking a balance: fungal commensalism versus pathogenesis. Curr Opin Microbiol 16:366-73
Iliev, Iliyan D; Funari, Vincent A; Taylor, Kent D et al. (2012) Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336:1314-7