Host immunity to commensal gut fungi

摘要/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健康方面的作用，人们知之甚少。 炎症性疾病。大多数对肠道微生物区系的研究都集中在共生细菌上，这些细菌占大多数。 肠道中的微生物。许多研究都证明了肠道细菌对调节粘膜的作用。 免疫和指导组织的发育和修复。抗生素的使用、宿主的遗传学和饮食影响着 细菌微生物区系与肠道炎症性疾病的易感性。那真菌呢？我们的整体 假说是肠道真菌失调影响免疫系统的方式可以增加 对炎症性疾病的易感性，并可以有针对性地增加对炎症性疾病的抵抗力。 在这项更新建议中，我们记录了小鼠中“正常”真菌生物群的破坏导致增加 易患结肠炎和过敏性哮喘。我们提出的研究旨在了解抗生素是如何使用的， 寄主遗传和饮食在近期和长期影响肠道真菌微生物区系(“真菌生物群”)。我们 将描述常见的(念珠菌和酵母菌)和不太知名的(壁球菌属和表皮菌属) 真菌影响肠道炎症性疾病的易感性。

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.