Host immunity to commensal gut fungi

宿主对共生肠道真菌的免疫力

• 批准号: 10160894
• 负责人: David M. Underhill
• 金额: $ 47.98万
• 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 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10160894
• 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; dextran sulfate sodium induced colitis; dietary; dysbiosis; fungal microbiota; fungus; gut microbiota; immune function; in vivo; inflammatory disease of the intestine; 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.

摘要/摘要 关于肠道真菌在调查健康的肠道菌群和贡献方面的作用知之甚少 炎症性疾病。肠道菌群的大多数研究都集中在构成大多数的共生细菌上 肠道中的微生物。大量研究记录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，宿主遗传学和饮食会影响 细菌菌群和对肠道炎症性疾病的敏感性。那真菌呢？我们的整体 假设是，肠道真菌营养不良会以增加的方式影响免疫系统 对炎症性疾病的敏感性，可以针对增加对炎症性疾病的抗性。 在此续签建议中，我们记录了小鼠中“正常”的霉菌组的破坏会增加 对结肠炎和过敏性哮喘的敏感性。我们提出的研究旨在了解抗生素的使用方式， 寄主遗传学和饮食会在近期和长期内影响肠道真菌微生物群（“ Mycobiota”）。我们 将表征如何普遍（念珠菌和糖疗法）和鲜为人知（wallamia，epicoccum） 真菌影响对肠道炎症性疾病的敏感性。

项目成果

Striking a balance: fungal commensalism versus pathogenesis.

• DOI: 10.1016/j.mib.2013.05.004
• 发表时间: 2013-06
• 期刊: Current opinion in microbiology
• 影响因子: 5.4
• 作者: Iliev ID;Underhill DM
• 通讯作者: Underhill DM

Mycobiome: Approaches to analysis of intestinal fungi.

• DOI: 10.1016/j.jim.2015.04.004
• 发表时间: 2015-06
• 期刊: JOURNAL OF IMMUNOLOGICAL METHODS
• 影响因子: 2.2
• 作者: Tang, Jie;Iliev, Iliyan D.;Brown, Jordan;Underhill, David M.;Funari, Vincent A.
• 通讯作者: Funari, Vincent A.

The mycobiota: interactions between commensal fungi and the host immune system.

• DOI: 10.1038/nri3684
• 发表时间: 2014-06
• 期刊: Nature reviews. Immunology

Commensal Fungi in Health and Disease.

• DOI: 10.1016/j.chom.2017.07.002
• 发表时间: 2017-08-09
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: Limon JJ;Skalski JH;Underhill DM
• 通讯作者: Underhill DM