Host immunity to commensal gut fungi

宿主对共生肠道真菌的免疫力

• 批准号: 9598612
• 负责人: David M. Underhill
• 金额: $ 47.68万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9598612
• 关键词: Anti-Bacterial Agents; Antibiotics; Antifungal Agents; Awareness; Bacteria; Candida; Candida albicans; Cardiovascular Diseases; Cells; Colitis; Defect; Development; Diabetes Mellitus; Diet; Disease; Extrinsic asthma; Fatty acid glycerol esters; Genes; Genetic; Growth; Health; High Fat Diet; Homeostasis; Human; Immune; Immune response; Immune system; Immunity; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Intestines; Link; Lung diseases; Measures; Mediating; Microbe; Modeling; Mucosal Immunity; Mus; Oral; Patients; Population; Predisposition; Recombinant DNA; Resistance; Role; Saccharomyces; Saccharomyces cerevisiae; Saccharomycetales; Severities; Tissues; Variant; bacteriome; commensal bacteria; dysbiosis; fungal microbiota; fungus; gut microbiota; immune function; in vivo; member; microbiota; mouse model; mycobiome; repaired

SUMMARY/ABSTRACT 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.

总结/摘要 关于肠道真菌在调节健康肠道微生物区系和促进肠道微生物生长方面的作用， 炎症性疾病大多数肠道菌群的研究集中在肠道细菌，占大多数 肠道中的微生物许多研究已经证明了肠道细菌对调节粘膜的影响， 免疫和指导组织发育和修复。抗生素使用、宿主遗传学和饮食影响 细菌微生物群和对肠道炎性疾病的易感性。真菌呢我们的整体 一种假说是肠道真菌生态失调影响免疫系统， 其可被靶向以增加对炎性疾病的抗性。 在这项更新提案中，我们记录了小鼠中“正常”真菌生物群的破坏导致增加的 易患结肠炎和过敏性哮喘。我们建议进行旨在了解抗生素使用， 宿主遗传学和饮食在近期和长期影响肠道真菌微生物群（“真菌生物群”）。我们 将描述常见（念珠菌属和酵母菌属）和不太知名（瓦耳菌属、Epicoccum） 真菌影响对肠道炎性疾病的易感性。