Understanding mechanisms by which microbial strains and metabolites in fermented foods decrease systemic inflammation

了解发酵食品中的微生物菌株和代谢物减少全身炎症的机制

• 批准号: 10611939
• 负责人: Matthew Raymond Olm
• 金额: $ 5.19万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10611939
• 关键词: Acute Disease; Adult; Animal Model; Antiinflammatory Effect; Bioinformatics; Blood specimen; Cells; Chronic; Chronic Disease; Complex; Computational Biology; Consumption; Data; Developed Countries; Development; Diabetes Mellitus; Diet; Dietary Intervention; Disease; Elements; Experimental Models; Fermentation; Food; Genetic Induction; Germ-Free; Gnotobiotic; Goals; Guidelines; Health; Heart Diseases; Human; Immune; Immune System Diseases; Immune system; Immunologics; Inflammation; Inflammatory; Intervention; Intervention Studies; Intervention Trial; Intestines; Learning Skill; Link; Location; Lymphoid Cell; Malignant Neoplasms; Medicine; Mentors; Metabolic; Metabolite Interaction; Metagenomics; Microbe; Mus; Precision therapeutics; Recording of previous events; Regulation; Regulatory T-Lymphocyte; Research; Resolution; Sampling; Sampling Studies; Series; Serum; Signal Transduction; Technology; Testing; Universities; Yogurt; cytokine; dietary guidelines; dysbiosis; evidence base; experience; experimental study; food consumption; gut inflammation; gut microbiome; gut microbiota; host microbiome; immunoregulation; improved; inflammatory marker; metabolomics; microbial; microbiome; microbiome analysis; microbiota; mouse model; prevent; reconstitution; systemic inflammatory response

Project Summary Chronic inflammation is common in developed countries and is associated with the development of cancer, heart disease, and diabetes. Chronic inflammation is caused by immune dysregulation and has been linked to dysbiotic, low diversity gut microbiotas. Dietary intervention has shown promise in the treatment of these disorders, but the mechanisms underlying this effect are unclear and which type of foods will be effective are under debate. This project leverages collected samples and data from a recently conducted fermented food (yogurt, sauerkraut, kimchi, etc.) dietary intervention study in healthy adults, in which inflammatory markers decreased over the course of the intervention. Here, I will perform high resolution metagenomic, metabolomic, and immune profiling on fecal and blood samples from this study to better understand the extent and basis of fermented foods impacting the human immune system and endogenous microbiome (Aim 1), and additionally perform a series of highly-controlled mouse experiments to determine the specific components of fermented foods that are responsible for immune modulating effects (Aim 2). My previous experience in computational biology and bioinformatics make me well-equipped to analyze the large amount of data that will be generated, and the expertise in animal models for microbiome analysis, immunological profiling, and metabolomic analysis honed by my mentoring team make Stanford University an ideal location to learn the skills I will need to perform the technical experiments. Completion of these aims will generate a detailed understanding of the effects that fermented foods have on the mammalian immune system and endogenous microbiome, identify specific microbial strains and metabolites associated with decreased inflammation in humans, and establish the specific components of fermented foods that improve immune system regulation, paving the way for evidence-based guidance on the consumption of fermented foods and the development of precision therapeutics to reduce chronic inflammation and prevent acute disease.

项目摘要 慢性炎症在发达国家很常见，与癌症、心脏病、 疾病和糖尿病。慢性炎症是由免疫失调引起的， 微生态失调，低多样性的肠道微生物。饮食干预已显示出治疗这些疾病的希望。 疾病，但这种影响的机制尚不清楚，哪种类型的食物将是有效的， 正在讨论中。该项目利用从最近进行的发酵食品中收集的样品和数据 （酸奶、泡菜、泡菜等）健康成人的饮食干预研究，其中炎症标志物 在干预过程中下降。在这里，我将进行高分辨率的宏基因组，代谢组， 和免疫分析，以更好地了解 发酵食品影响人体免疫系统和内源性微生物组（目标1）， 进行了一系列高度对照的小鼠实验，以确定发酵的具体成分， 负责免疫调节作用的食物（目标2）。我以前在计算方面的经验 生物学和生物信息学使我能够很好地分析将产生的大量数据， 以及微生物组分析、免疫学分析和代谢组学分析的动物模型方面的专业知识 经过我的导师团队的磨练，斯坦福大学成为了我学习工作技能的理想场所 技术实验。完成这些目标将产生一个详细的了解的影响， 发酵食品对哺乳动物免疫系统和内源性微生物组的影响， 微生物菌株和代谢产物与人类炎症减少有关，并建立了特异性 发酵食品的成分，改善免疫系统调节，为循证医学铺平道路 指导发酵食品的消费和精确疗法的发展，以减少 慢性炎症和预防急性疾病。