Liberation of Plant Nutrients by the Gut Microbiota

肠道微生物群释放植物营养素

• 批准号: 8572895
• 负责人: Elizabeth Susan Sattely
• 金额: $ 240万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-30 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8572895
• 关键词: Anti-Inflammatory Agents; Anti-inflammatory; Biochemistry; Biological; Biological Factors; Carbohydrates; Chemicals; Collaborations; Communities; Diet; Disease; Glucosinolates; Gnotobiotic; Harvest; Health; Human; Immunology; Mediating; Metabolic Pathway; Metabolism; Microbe; Microbiology; Molecular; Nutrient; Outcome; Pharmaceutical Preparations; Plants; Process; Source; Stream; Work; absorption; base; disorder prevention; experience; gut microbiota; gut microflora; insight; microbial; microbial community; mouse model; novel; small molecule

DESCRIPTION (provided by applicant): The diet is our sole source of nutrients, yet we are just beginning to understand how the human gut microbiota acts as an essential layer of metabolism. Resident microbes not only help to capture plant-derived carbohydrates from our diet, but also likely encounter (and modify) a steady stream of drug-like molecules from plants, a number of which are known to have important biological activity in humans (e.g. anti-inflammatory isoflavonoids and chemo preventative glucosinolates). We propose that these plant-derived small molecules mediate plant-microbe interactions not only in the rhizosphere, but also in the human gut. In this capacity, dietary compounds from plants might represent the most important environmental perturbation regularly experienced by the gut microbiota. Furthermore, we suggest that sensing and processing of dietary plant molecules by the gut microbiota generates compounds with enhanced biological activities, and therefore functions as a central mechanism for diet-based disease prevention. This project will characterize in molecular detail key plant-microbe interactions that take place in the human gut, and will elucidate the mechanisms by which gut microbes directly influence the absorption of 'plant drugs' from diet. Specific outcomes of this project will be insight into (1) how key dietary small molecules with known biological activity are processed, activated, and presented by gut microflora to the human host, and (2) how these metabolites impact microbial community dynamics in the gut. Our proposed experimental approach will draw on our expertise in chemical analysis, natural products biochemistry, and metabolic pathways. This work will be carried out in collaboration with the Sonnenburg lab in Microbiology and Immunology at Stanford who will contribute experience in gut microbiota community dynamics and gnotobiotic mouse models. We anticipate that the identification of how key dietary plant-derived molecules impact gut microbial species will enable the reprogramming of gut metabolism to maximize nutrient harvest and create a novel means of controlling a microbial niche that has a direct effect on human health and disease.

描述（由申请人提供）：饮食是我们唯一的营养来源，但是我们才开始了解人类肠道微生物群如何充当代谢的重要层。常驻的微生物不仅有助于从我们的饮食中捕获植物来源的碳水化合物，而且很可能会遇到（并修改）植物中稳定的药物样分子流，其中许多人在人类中具有重要的生物学活性（例如，抗炎异黄酮和化学预防性糖醇）。我们建议这些植物衍生的小分子不仅在根际，而且在人类肠道中介导植物 - 微生物相互作用。以这种能力，植物的饮食化合物可能代表了肠道菌群经常经历的最重要的环境扰动。此外，我们建议肠道菌群对饮食植物分子进行感测和加工会产生具有增强的生物学活性的化合物，因此起着基于饮食疾病的预防的中心机制。该项目将以分子细节为特征，关键的人类肠道中发生的植物微生物相互作用，并将阐明肠道微生物直接影响饮食中“植物药物”的吸收的机制。该项目的具体结果将深入了解（1）肠道微生物对人类宿主的处理，激活和提出的关键饮食小分子如何对人类宿主进行处理，激活和提出，以及（2）这些代谢物如何影响肠道中的微生物群落动力学。我们提出的实验方法将利用我们在化学分析，天然产品生物化学和代谢途径方面的专业知识。这项工作将与斯坦福大学的微生物学和免疫学实验室合作进行，他们将在肠道微生物群社区动力学和gnotobiotic鼠标模型中贡献经验。我们预计，鉴定关键饮食植物衍生的分子如何影响肠道微生物物种将使肠道代谢重新编程以最大程度地提高营养收获，并创建一种具有直接效果的微生物细分市场的新颖手段 关于人类健康和疾病。