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Mechanisms of fungal involvement during intestinal disease

肠道疾病期间真菌参与的机制

基本信息

批准号：
10615244
负责人：
June Louise Round
金额：
$ 44.59万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-08 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10615244
关键词：
Affect Allopurinol Animals Antibodies Archaea Area Autophagocytosis Cell Wall Cells Clinical Colitis Communities Complex Crohn&apos s disease Data Defect Development Diagnostic Disease Disease Progression Environmental Risk Factor Epithelium Exposure to Genes Genetic Genetic Polymorphism Health Human Immune Immune response Immune system Immunity Immunology Individual Inflammatory Bowel Diseases Intestinal Diseases Intestines Knowledge Lead Link Literature Maintenance Metabolic Pathway Metabolism Microbe Molecular Mucous Membrane Mutation Myelogenous Myeloid Cells Pathway interactions Patient Care Patients Permeability Pharmaceutical Preparations Physiology Play Population Process Production Publishing Purines Reporting Research Personnel Role Saccharomyces cerevisiae Serum Severity of illness Signal Transduction Susceptibility Gene Testing Up-Regulation Uric Acid Viral Work Yeasts commensal microbes dectin 1 diagnostic tool disorder risk experimental study fungal genetics fungal microbiota fungus genetic risk factor gut health high risk human microbiota improved intestinal epithelium intestinal homeostasis member microbiota mycobiome neglect purine metabolism receptor response therapeutic target trafficking

项目摘要

Abstract The commensal microbiota has important impacts on host physiology and health that are only beginning to be elucidated. Most current studies, however, have focused only on the bacterial microbiota despite the presence of fungal, archaeal and viral members. The presence of anti-Saccharomyces cerevisiae (ASCA) antibodies serves as a diagnostic tool for Crohn’s disease (CD) and suggests that fungal members of the microbiota contribute to disease severity. Moreover, common genetic polymorphisms identified in individuals with IBD, such as Nod2, Dectin-1, and Card9 are known to recognize fungal cell wall components. We have recently demonstrated that one of the most prominent members of the mycobiota, S. cerevisiae, can exacerbate intestinal colitis through upregulation of host purine metabolism in the gut. The end product of purine metabolism in humans is uric acid. Recent studies have demonstrated that uric acid can have significant impacts on autophagy. Coincidentally, many of the genes associated with IBD in humans, impact autophagic processes. There is a significant body of clinical literature that links autophagy, yeast, and uric acid production, yet these relationships have yet to be explored. Here we propose to identify how fungal members of the microbiota induce purine metabolism from intestinal epithelia and determine how purine metabolism influences intestinal immunity to worsen disease. We have brought together an inter-disciplinary team of investigators with combined expertise in autophagy, fungal genetics and mucosal immunology to explore how yeast can functionally influence intestinal disease.

摘要