Collaborative Research: The role of gut microbiota in supplying amino acids to their mammalian hosts

合作研究：肠道微生物群在向哺乳动物宿主提供氨基酸方面的作用

• 批准号: 1755353
• 负责人: Marilyn Fogel
• 金额: $ 37.12万
• 依托单位: University of California-Riverside
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755353&HistoricalAwards=false
• 关键词: Collaborative; Research; role; gut; microbiota

Microbes living in digestive tracks are now recognized as important contributors to the health and fitness of animals. Within a single host, thousands of different microbial species form symbiotic communities influenced by many factors, including host diet. These communities often metabolize compounds that their hosts cannot, and likely supply essential compounds needed for growth and reproduction, particularly for organisms that experience protein limitation. To date, the role the gut microbiome plays in the protein metabolism of its hosts has not been systematically explored. This project will combine studies of the building blocks of proteins (amino acids), stable isotope techniques, and next generation DNA sequencing to answer two questions. First, how does gut microbiome contribute to the building and maintenance of tissues by its hosts? And second, which microbial species are most important in the gut? In addition, a series of controlled feeding experiments where the diet will be systematically varied will also determine the role that the gut microboime plays in the relationship between hosts and the resources they consume. This work will provide many opportunities for training STEM students through hands-on experiences. These experiences are important for young scientists as they gain confidence and nurture identities as independent researchers. University of New Mexico and University of California at Riverside are both minority-majority universities and certified Hispanic Serving Institutions. The research group will also host two workshops to discuss how animal and microbial ecologists can work together to study interactions between gut microbes and their host organisms.Gut microbiota are integral components contributing to the health and fitness of animals. Animal ecologists and eco-physiologists are discovering the many positive and negative roles microbes play in contributing to their hosts. Within a single host, thousands of different microbial species form symbiotic communities influenced by many factors, including host diet. These communities often metabolize compounds that their host species cannot, and likely supply essential compounds needed for homeostasis and reproduction, particularly for organisms that experience seasonal diet stress or protein limitation. This project will combine studies of amino acids using stable isotope techniques coupled with next generation genetic sequencing to (1) identify and potentially quantify, the degree to which the gut microbiome contributes to protein budgets and the building and maintenance of tissues by its hosts, and (2) characterize which microbial taxa are most closely associated with digestive metabolisms in the gut, in which amino acids are used subsequently by the host to synthesize tissues. These topics will be addressed through a series of controlled feeding experiments on deer mice where the proportion and isotopic compositions of dietary macromolecules and individual compounds will be systematically varied. The study will produce a more thorough understanding of the role that the gut microboime plays in influencing natural isotope tracers, a tool for quantifying diet composition and trophic level of wild animals. The research group will also host two workshops to discuss how animal and microbial ecologists can combine genetic and isotopic data to study biochemical interactions between gut microbes and their host organisms.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

生活在消化轨道上的微生物现在被认为是动物健康和体能的重要贡献者。在一个宿主内，数千个不同的微生物物种在许多因素的影响下形成共生群落，包括宿主的饮食。这些群落经常代谢宿主无法代谢的化合物，并可能提供生长和繁殖所需的必要化合物，特别是对于经历蛋白质限制的生物体。到目前为止，肠道微生物群在宿主蛋白质代谢中的作用还没有得到系统的研究。这个项目将结合对蛋白质(氨基酸)的构建块、稳定同位素技术和下一代DNA测序的研究来回答两个问题。首先，肠道微生物群如何对宿主组织的构建和维护做出贡献？第二，肠道中最重要的微生物种类是什么？此外，一系列有系统地改变饮食的控制喂养实验也将确定肠道微生物群在宿主与其消耗的资源之间的关系中所起的作用。这项工作将为通过实践经验培训STEM学生提供许多机会。这些经历对年轻科学家来说很重要，因为他们获得了信心，并培养了作为独立研究人员的身份。新墨西哥大学和加州大学河滨分校都是少数族裔占多数的大学，都是经过认证的拉美裔服务机构。该研究小组还将主办两个研讨会，讨论动物和微生物生态学家如何合作，研究肠道微生物与其宿主组织之间的相互作用。肠道微生物区系是促进动物健康和健身的不可或缺的组成部分。动物生态学家和生态生理学家正在发现微生物在帮助宿主方面扮演着许多积极和消极的角色。在一个宿主内，数千个不同的微生物物种在许多因素的影响下形成共生群落，包括宿主的饮食。这些群落经常代谢寄主物种无法代谢的化合物，并可能提供动态平衡和繁殖所需的必要化合物，特别是对于经历季节性饮食压力或蛋白质限制的生物体。该项目将结合使用稳定同位素技术和下一代基因测序对氨基酸的研究，以(1)识别并潜在地量化肠道微生物组对蛋白质收支以及宿主组织的建立和维护的贡献程度，以及(2)表征哪些微生物分类群与肠道中的消化代谢关系最密切，其中氨基酸随后被宿主用来合成组织。这些主题将通过在鹿小鼠身上进行的一系列受控喂养实验来解决，在这些实验中，饮食大分子和单个化合物的比例和同位素组成将发生系统的变化。这项研究将对肠道微生物在影响天然同位素示踪剂中所起的作用产生更彻底的理解，天然同位素示踪剂是一种量化野生动物饮食组成和营养水平的工具。该研究小组还将主办两次研讨会，讨论动物和微生物生态学家如何结合遗传和同位素数据来研究肠道微生物与其宿主组织之间的生化相互作用。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。