Liberation of Plant Nutrients by the Gut Microbiota

描述（由申请人提供）：饮食是我们唯一的营养来源，然而我们才刚刚开始了解人类肠道微生物群如何作为新陈代谢的基本层。常驻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，而且可能会遇到（并修改）来自植物的稳定的药物样分子流，其中许多已知对人类具有重要的生物活性（例如抗炎异黄酮和化学预防硫代葡萄糖苷）。我们认为这些源自植物的小分子不仅在根际，而且在人体肠道中介导植物与微生物的相互作用。在这种情况下，来自植物的膳食化合物可能代表了肠道微生物群经常经历的最重要的环境扰动。此外，我们认为肠道微生物群对膳食植物分子的感知和加工产生了具有增强生物活性的化合物，因此是饮食疾病预防的核心机制。该项目将在分子细节上描述发生在人类肠道中的关键植物-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”吸收的机制。该项目的具体成果将深入了解(1)具有已知生物活性的关键膳食小分子如何被肠道菌群加工、激活并呈现给人类宿主，以及(2)这些代谢物如何影响肠道微生物群落动态。我们提出的实验方法将利用我们在化学分析、天然产物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微生物学和免疫学Sonnenburg实验室合作进行，该实验室将在肠道微生物群落动态和非生物小鼠模型方面提供经验。我们预计，确定关键的膳食植物源分子如何影响肠道微生物物种，将使肠道代谢的重编程能够最大化营养收获，并创造一种新的方法来控制具有直接影响的微生物生态位

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.