Physiology of bacterial metabolism in the human gut microbiome

摘要： 在我们对人类肠道微生物群的了解中，最大的差距之一是微生物如何获得能量 以及维持它们生长所需的营养物质。这是一个重要的缺陷，因为微生物 途径产生短链脂肪酸，如丁酸，吲哚，如吲哚丙酸，和胺，如 三甲胺，所有这些都在寄主生理和疾病中发挥关键作用。了解新陈代谢 微生物制造这些分子的基础过程对于制定可预测的策略至关重要 控制肠道微生物区系的代谢产出。 尽管肠道中的微生物新陈代谢对人类生理学很重要，但我们对 这些代谢途径的性质。知识中的一个关键差距是高丰度代谢物的途径 与共生细菌的生理学有关。了解这些新陈代谢策略对于 制定旨在可预测地调节肠道微生物区系代谢产出的策略。其中一个 研究肠道微生物区系的主要挑战是遗传工具只适用于一小部分 细菌。因此，迫切需要新的工具来研究基因的生理和代谢。 难对付的微生物。 在这个项目中，我们将使用细菌生理学和遗传学的技术来揭示肠道中的微生物是如何 从饮食营养素中获取能量，以及这些过程如何有助于产生类似药物的小分子 影响寄主生理。我们还将开发一种新的代谢组学方法来生成全基因组图谱 在遗传上易驯化和难治的肠道细菌中微生物小分子的遗传决定因素。这些 研究将提供对微生物组的几个核心功能的基本见解，并将刺激 未来研究人类肠道微生物群的途径。

Summary: One of the biggest gaps in our knowledge of the human gut microbiome is how microbes secure the energy and nutrients required to sustain their growth. This is an important deficit in light of the fact that microbial pathways produce short chain fatty acids like butyrate, indoles like indolepropionic acid, and amines like trimethylamine, all of which play a critical role in host physiology and disease. Understanding the metabolic processes that underlie why microbes make these molecules is critical for developing strategies to predictably control the metabolic output of the gut microbiota. Despite the importance of microbial metabolism in the gut to human physiology, we know very little about the nature of these metabolic pathways. A key gap in knowledge is how pathways for high abundance metabolites is linked to the physiology of commensal bacteria. Knowledge of these metabolic strategies is critical to developing strategies aimed at predictably modulating the metabolic output of the gut microbiota. One of the major challenges to studying the gut microbiota is that genetic tools are only available for a small subset of bacteria. Therefore, new tools are urgently needed to study the physiology and metabolism of genetically intractable microbes. In this project, we will use techniques in bacterial physiology and genetics to uncover how microbes in the gut capture energy from dietary nutrients, and how these processes contribute to drug-like small molecules that influence host physiology. We will also develop a new metabolomics approach to generate genome-wide maps of genetic determinants of microbial small molecules in genetically tractable and intractable gut bacteria. These studies will provide fundamental insights into several of the microbiome's core functions and will stimulate future avenues for inquiry into the human gut microbiome.