Liberation of Plant Nutrients by the Gut Microbiota

描述(申请人提供)：饮食是我们唯一的营养来源，但我们才刚刚开始了解人类肠道微生物区系如何作为新陈代谢的必要层。寄生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(并修饰)来自植物的稳定的类药物分子，其中一些已知对人类具有重要的生物活性(例如抗炎异黄酮类化合物和化学预防硫代葡萄糖苷)。我们认为，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与微生物的相互作用。在这种能力下，来自植物的饮食化合物可能是肠道微生物区系经常经历的最重要的环境扰动。此外，我们认为，肠道微生物区系对饮食植物分子的感知和处理产生了具有增强生物活性的化合物，因此作为基于饮食的疾病预防的中心机制。这个项目将详细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从饮食中吸收“植物药物”的机制。该项目的具体成果将是深入了解(1)具有已知生物活性的关键饮食小分子是如何被处理、激活并由肠道微生物区系呈现给人类宿主的，以及(2)这些代谢物如何影响肠道微生物群落的动态。我们建议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Sonnenburg微生物学和免疫学实验室合作进行，该实验室将在肠道微生物区系群落动力学和GnotoBiotic小鼠模型方面贡献经验。我们预计，确定关键的饮食植物衍生分子如何影响肠道微生物物种将使肠道新陈代谢重新编程，以最大限度地获取营养，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。 关于人类健康和疾病。

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.