Gut Microbial Factors in Farming Lifestyle and Allergic Sensitization

农业生活方式和过敏致敏中的肠道微生物因素

• 批准号: 10633368
• 负责人: Jose C Clemente
• 金额: $ 31.77万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-07 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633368
• 关键词: Acceleration; Affect; Allergic; Allergic rhinitis; Animal Model; Anti-Allergic Agents; Anti-Inflammatory Agents; Asthma; Atopic Dermatitis; Bacteria; Bifidobacterium; Bile Acids; Bioinformatics; Biological Markers; Catabolism; Child; Childhood; Chronic; Colon; Communities; Consultations; Data Analyses; Development; Dietary Fiber; Disease; Early identification; Epithelium; Exposure to; Farm; Fermentation; Food Hypersensitivity; Future; Genes; Goals; Health; Hypersensitivity; Immune; Immune system; Immunity; Immunocompetence; Immunologic Markers; Indoles; Infant; Intervention; Intestinal permeability; Lactic acid; Lamina Propria; Life; Life Style; Measures; Medical; Mennonite; Metabolism; Metadata; Methods; Outcome; Pathway interactions; Permeability; Play; Prevalence; Prevention strategy; Primary Prevention; Production; Property; Publishing; Regulatory T-Lymphocyte; Risk; Risk Reduction; Role; Sampling; Shotgun Sequencing; Symptoms; T cell differentiation; Taxonomy; Testing; Time; Tryptophan; Tryptophan Metabolism Pathway; Urban Community; Volatile Fatty Acids; Work; atopy; bacterial community; bile acid metabolism; biobank; biomarker identification; cohort; data integration; data management; fecal metabolome; gut microbiome; high risk infant; improved; interleukin-22; metabolome; metabolomics; microbial; microbiome; microbiome composition; microbiome research; novel; oral tolerance; rational design; skin barrier; skin microbiome; suburb

PROJECT SUMMARY/ABSTRACT – PROJECT 1 Atopic diseases, including atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma, are the most common chronic medical conditions affecting children in the US, and prevention strategies remain largely unsuccessful. While the risk of asthma is reduced in infants with a farming lifestyle, which includes exposure to a diverse microbiome in early life, the microbial mechanisms of protection against AD and FA under this lifestyle are still being investigated. Multiple bacterial metabolites have been also explored for their connection with atopic disease: short-chain fatty acids (SCFA), which can induce the differentiation of anti-inflammatory colonic Tregs, tryptophan metabolism, which modulates epithelial barrier permeability, or bile acids, which regulate T-cell differentiation in the lamina propria. Our published and preliminary results demonstrate that, compared to infants from urban/suburban Rochester (ROC), the traditional agrarian community of Old Order Mennonites (OOM) are protected against atopic diseases and harbor a distinct gut bacterial community, including an enrichment in Bifidobacteria and Clostridia species, suggesting that lifestyle and early life microbiome accelerate immunocompetence and might play a protective role in atopic diseases. The goals of this proposal are to determine how the gut microbiome and its byproducts develop in infants to modulate the risk of atopic diseases, to identify microbial and metabolite biomarkers to screen high-risk infants, and to assess mechanisms associated with protective innate and adaptive immune markers and skin barrier integrity and microbiome by integration of data with Projects 2 and 3. Our central hypothesis is that the microbiome of infants who do not develop AD and FA modulates the bacterial metabolite pool that confers protection or risk of atopic disease. We hypothesize that the gut microbiome of non-atopic urban Rochester infants and OOM infants will be enriched in species with anti-inflammatory properties and genes related to short-chain fatty acid production, lactic acid metabolism, and tryptophan and bile acid metabolism, as well as an accelerated gut microbiome maturation compared with atopic infants. In parallel, we will also assess the fecal metabolome of OOM and ROC infants, and test its association with atopic outcomes: we hypothesize that tryptophan, short-chain fatty acids and bile acids will be differential between atopic and non-atopic infants, and that correlations between microbiome and metabolome will also be differential based on health outcomes. Finally, we will evaluate the longitudinal development of the gut microbiome and metabolome to identify groups of infants with similar changes over time that are associated with atopic disease, as well as with biomarkers from Projects 2 and 3. The rational design of our strategy will identify novel bacterial and metabolite biomarkers that are associated with protection or risk of atopic disease, and which will facilitate the development of microbial interventions in the future.

项目总结/摘要-项目1 特应性疾病，包括特应性皮炎（AD）、食物过敏（FA）、过敏性鼻炎和哮喘，是最常见的疾病。 在美国，影响儿童的常见慢性疾病和预防策略仍然主要是 不成功。虽然有农业生活方式的婴儿患哮喘的风险降低， 早期生活中的微生物组多样性，在这种生活方式下预防AD和FA的微生物机制 仍在调查中多种细菌代谢物也被探索与特应性 疾病：短链脂肪酸（SCFA），它可以诱导抗炎结肠炎的分化， 色氨酸代谢，调节上皮屏障通透性，或胆汁酸，调节T细胞 固有层的分化。我们发表的初步结果表明，与婴儿相比， 从城市/郊区罗切斯特（ROC），传统的农业社区旧秩序门诺派（OOM）是 保护免受特应性疾病，并拥有独特的肠道细菌群落，包括富集 双歧杆菌和梭菌属物种，表明生活方式和早期生活微生物组加速 免疫活性，并可能发挥保护作用的特应性疾病。本提案的目标是 确定肠道微生物组及其副产物如何在婴儿中发育以调节特应性疾病的风险， 确定微生物和代谢物生物标志物，以筛查高危婴儿，并评估相关机制 与保护性先天性和适应性免疫标志物和皮肤屏障完整性和微生物组的整合， 项目2和项目3的数据。我们的中心假设是，没有发育的婴儿的微生物组 AD和FA调节细菌代谢物库，其赋予特应性疾病的保护或风险。我们 假设非特应性城市罗切斯特婴儿和OOM婴儿的肠道微生物组将富含 具有抗炎特性的物种和与短链脂肪酸产生、乳酸 代谢，色氨酸和胆汁酸代谢，以及加速的肠道微生物组成熟 与特应性婴儿相比。同时，我们还将评估OOM和ROC婴儿的粪便代谢组， 并测试其与特应性结局的关系：我们假设色氨酸、短链脂肪酸和胆汁酸 过敏性和非过敏性婴儿之间的酸是不同的，微生物组和 代谢组也将基于健康结果而不同。最后，我们将评估纵向 开发肠道微生物组和代谢组，以确定随时间推移发生类似变化的婴儿群体 与特应性疾病相关的，以及与项目2和3的生物标志物相关的。的合理设计 我们的战略将确定新的细菌和代谢物的生物标志物，与保护或风险， 特应性疾病，这将促进未来微生物干预的发展。