MTM 2: The rules of microbiota colonization of the mammalian gut

MTM 2：哺乳动物肠道微生物群定植规则

• 批准号: 2025515
• 负责人: Georg Gerber
• 金额: $ 290万
• 依托单位: Brigham & Women's Hospital Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2025515&HistoricalAwards=false
• 关键词: MTM; rules; microbiota; colonization; mammalian

Microbiomes, or the collections of trillions of bacteria and other micro-organisms living on, within and around us, have enormous impact on human life. For example, they help people digest food, promote the growth of farm animals and crops, and degrade pollutants in the environment. Despite the importance of microbiomes, the processes governing their formation and maintenance remain poorly understood. The mammalian gut is a particularly intriguing system for microbiome studies, since a diverse collection of microbes has evolved that specifically colonizes and functions in that environment. The goal of the project is to derive fundamental rules that describe and predict the dynamic process of microbial colonization of the mammalian gut. To achieve this goal, the team of investigators will develop new computer-based methods to automatically extract predictive and explanatory rules from large microbiome data sets. The team will also develop new experimental tools and generate data sets in mouse measuring how microbiomes change over time and across space in the mammalian gut. Overall, the project will further the understanding of the formation of microbiomes in mammals and can provide broader insights into the emergence of other microbial ecosystems, such as those in soil and marine environments. These insights could ultimately help scientists to rationally alter or maintain microbiomes in different environments to benefit human activities. The project will also generate practical resources for the scientific community (computer-based tools and datasets) and provide education on the microbiome to college and elementary school students through courses and hands-on labs.A wealth of genomic data provides information as to which microbes are present in environments, but little insight into underlying factors that explain or predict complex assemblages of microbial consortia. This project aims to elucidate mechanistic factors that drive the dynamic process of microbial colonization of the mammalian gut. These determinants will be investigated at multiple systems scales, from the level of microbial communities down to the level of individual genes. The project will leverage high-throughput experimental methods developed by the investigators, to generate data characterizing functional genetic selection and spatial organization of microbiota in the mammalian gut. From the Computer Science perspective, the project will develop new computational methods to infer human-interpretable rules and other structured outputs from complex and noisy high-throughput microbiome datasets, using Bayesian and neural-style approaches that incorporate prior biological knowledge while scaling to massive datasets. This project has three main thrusts: 1) Learn microbial community-level rules that quantitatively predict population dynamics of mouse gut colonization and assess these rules across differing ranges of microbial diversity and composition, 2) Elucidate microbial gene-level mechanisms that predict mouse gut colonization dynamics, and 3) Profile microbial spatiotemporal organization and dynamics during gut colonization at the species and gene level to predict microbial community dynamics. The project is expected to establish a set of new computational and experimental tools and principles for understanding the rules of microbial colonization of the gut, with potential applications to other ecosystems including gut microbiota of non-mammalian species as well as complex environmental microbiota.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.

微生物组或我们周围和周围的其他微生物的收集对人类的生活产生了巨大影响。例如，它们可以帮助人们消化食物，促进农场动物和农作物的生长，并在环境中降解污染物。尽管微生物组很重要，但管理其形成和维护的过程仍然知之甚少。哺乳动物的肠道是微生物组研究的特别有趣的系统，因为多种微生物的集合已经进化出来，在该环境中专门殖民和功能。该项目的目的是得出描述和预测哺乳动物肠道微生物定植的动态过程的基本规则。为了实现这一目标，研究人员将开发新的基于计算机的方法，以自动从大型微生物组数据集中提取预测性和解释规则。该团队还将开发新的实验工具，并在鼠标中生成数据集，以测量微生物的时间随时间和跨哺乳动物肠道的空间的变化。总体而言，该项目将进一步了解哺乳动物中微生物的形成，并可以为其他微生物生态系统（例如土壤和海洋环境中的哺乳动物的出现）提供更广泛的见解。这些见解最终可以帮助科学家合理地改变或维护不同环境中的微生物，以使人类活动受益。该项目还将为科学界（基于计算机的工具和数据集）创造实用资源，并通过课程和动手实验室为大学和小学生提供有关微生物组的教育。大量的基因组数据提供了信息，提供了在环境中存在微生物的信息，但对基本因素的洞察力很少，这些因素很少解释或预测微生物协会的复杂组合。该项目旨在阐明驱动哺乳动物肠道微生物定植动态过程的机理因素。这些决定因素将在多个系统量表中从微生物群落的水平到单个基因的水平进行研究。该项目将利用研究人员开发的高通量实验方法，以生成表征哺乳动物肠道中微生物群的功能性遗传选择和空间组织的数据。从计算机科学的角度来看，该项目将使用贝叶斯和神经风格的方法从复杂而嘈杂的高通量微生物组数据集中推断出人解剖规则和其他结构化输出，这些输出在扩展到大型数据集的同时结合了先前的生物学知识。 This project has three main thrusts: 1) Learn microbial community-level rules that quantitatively predict population dynamics of mouse gut colonization and assess these rules across differing ranges of microbial diversity and composition, 2) Elucidate microbial gene-level mechanisms that predict mouse gut colonization dynamics, and 3) Profile microbial spatiotemporal organization and dynamics during gut colonization at the species and gene level to predict microbial community动力学。预计该项目将建立一组新的计算和实验工具和原理，以理解肠道的微生物定殖规则，并可能应用于其他生态系统，包括非哺乳动物物种的肠道菌群以及复杂的环境微生物群，以及这一奖项。该奖项通过审查了值得评估的构成者的构成师，这是NSF的法规及其构成的范围。

项目成果

Microbiota imbalance induced by dietary sugar disrupts immune-mediated protection from metabolic syndrome.

• DOI: 10.1016/j.cell.2022.08.005
• 发表时间: 2022-09-15
• 期刊: CELL
• 影响因子: 64.5
• 作者: Kawano, Yoshinaga;Edwards, Madeline;Huang, Yiming;Bilate, Angelina M.;Araujo, Leandro P.;Tanoue, Takeshi;Atarashi, Koji;Ladinsky, Mark S.;Reiner, Steven L.;Wang, Harris H.;Mucida, Daniel;Honda, Kenya;Ivanov, Ivaylo I.
• 通讯作者: Ivanov, Ivaylo I.