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.

项目摘要/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，是最多的 影响美国儿童的常见慢性病状况，预防策略仍在很大程度上仍然 不成功。虽然患有农业生活方式的婴儿哮喘的风险降低，其中包括接触 潜水员在早期生命中的微生物组，在这种生活方式下，对AD和FA的保护机制 仍在调查中。还探索了多种细菌代谢产物的关系 疾病：短链脂肪酸（SCFA），可以诱导抗炎结肠的分化， 色氨酸代谢，调节上皮屏障的渗透性或胆汁酸，该溶质调节T细胞 固有椎板的分化。我们发表的初步结果表明，与婴儿相比 来自城市/郊区罗切斯特（ROC），传统的旧秩序农业社区（OOM）是 保护不受特应疾病的保护，并具有独特的肠道细菌群落，包括 双歧杆菌和梭状芽胞杆菌物种，表明生活方式和早期生命小体升高 免疫能力，可能在特应性疾病中起保护作用。该提议的目标是 确定肠道微生物组及其副产品如何在婴儿中发展以调节特应性疾病的风险， 鉴定微生物和代谢物生物标志物以筛查高风险婴儿，并评估相关的机制 通过集成 带有项目2和3的数据。我们的中心假设是不发展的婴儿的微生物组 AD和FA调节赋予特应性疾病的保护或风险的细菌代谢物池。我们 假设非原子城市罗切斯特婴儿和OOM婴儿的肠道微生物组将富含 具有抗炎特性和与短链脂肪酸，乳酸相关的基因的物种 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， 并测试其与特征结果的关联：我们假设色氨酸，短链脂肪酸和胆汁 酸在特应性和非原子婴儿之间是不同的，微生物组和微生物组之间的相关性 代谢组也将根据健康结果而差异。最后，我们将评估纵向 肠道微生物组和代谢组的开发，以识别随着时间的变化相似变化的婴儿群体 与特应性疾病以及项目2和3的生物标志物相关的。 我们的策略将确定与保护或风险相关的新型细菌和代谢物生物标志物 特应性疾病，这将促进未来微生物干预的发展。