Physiology of bacterial metabolism in the human gut microbiome

人类肠道微生物群中细菌代谢的生理学

• 批准号: 10623328
• 负责人: Dylan Dodd
• 金额: $ 39.73万
• 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: 2021-08-02 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10623328
• 关键词: Acids; Amines; Bacteria; Bacterial Physiology; Butyrates; Chromosome Mapping; Disease; Future; Genetic; Genetic Determinism; Growth; Health; Human; Indoles; Knowledge; Light; Link; Metabolic; Metabolic Control; Metabolic Pathway; Metabolism; Microbe; Nature; Nutrient; Nutritional Requirements; Output; Pathway interactions; Pharmaceutical Preparations; Physiology; Play; Process; Role; Secure; Techniques; Volatile Fatty Acids; bacterial genetics; bacterial metabolism; commensal bacteria; dietary; drug production; genome-wide; gut bacteria; gut microbiome; gut microbiota; insight; metabolic abnormality assessment; metabolomics; microbial; microbiome; small molecule; tool; trimethylamine

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.

概括： 我们对人类肠道微生物组知识的最大差距之一是微生物如何获取能量 以及维持其生长所需的营养。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，所有这些在宿主生理和疾病中都发挥着关键作用。了解新陈代谢 微生物产生这些分子的过程对于制定可预测的策略至关重要 控制肠道微生物群的代谢输出。 尽管肠道微生物代谢对人类生理学很重要，但我们对肠道微生物代谢知之甚少。 这些代谢途径的性质。知识的一个关键差距是高丰度代谢物的途径如何 与共生细菌的生理学有关。了解这些代谢策略对于 制定旨在可预测地调节肠道微生物群代谢输出的策略。中的一个 研究肠道微生物群的主要挑战是遗传工具仅适用于一小部分肠道微生物 细菌。因此，迫切需要新的工具来研究遗传物质的生理和代谢。 顽固的微生物。 在这个项目中，我们将利用细菌生理学和遗传学技术来揭示肠道微生物如何 从膳食营养素中捕获能量，以及这些过程如何产生类似药物的小分子 影响宿主生理。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 遗传易处理和难处理肠道细菌中微生物小分子的遗传决定因素。这些 研究将为微生物组的几个核心功能提供基本见解，并将刺激 探索人类肠道微生物组的未来途径。