Molecular interactions in the gut microbiota during early life colonization and perturbation

生命早期定植和扰动过程中肠道微生物群的分子相互作用

• 批准号: 10672321
• 负责人: Joseph Paul Zackular
• 金额: $ 44万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672321
• 关键词: Binding; Birth; Communities; Complex; Development; Dimensions; Disease; Ecosystem; Event; Gastrointestinal tract structure; Gnotobiotic; Goals; Health; Home; Image; Infant; Life; Maintenance; Maps; Mediating; Metabolic; Molecular; Newborn Infant; Organism; Play; Process; Resolution; Role; System; Technology; fitness; gut microbiota; innovation; member; metabolic abnormality assessment; metabolomics; microbial community; microbiota; microorganism; novel strategies; success

PROJECT SUMMARY The gastrointestinal tract is home to trillions of microorganisms that play an essential role in early life development and the maintenance of health. Shortly after birth, newborns are rapidly colonized by this complex microbial community that possesses a rich metabolic potential. Perturbation to assembly of the microbiota can have major downstream consequences to health. However, the fundamental ecological principles and molecular processes that underlie establishment of a beneficial and stable microbial community are largely unknown. Defining the multidimensional interactions in this complex ecosystem has proven incredibly challenging and has not moved far beyond simple associations. This is in part due to the inherent complexity and interconnectedness of the microbiota and a lack of fundamental mechanistic studies at this interface. Moreover, there are limited technologies available to spatially map and study metabolic cross talk between species in the microbiota. Here, we propose a novel strategy to generate a molecular blueprint of the metabolic interactions in the assembling microbiota using an innovative pipeline that integrates advanced imaging metabolomics with comprehensive mechanistic studies. Our objective is to generate a high-resolution spatial map of metabolites during community assembly and perturbation. We will use this molecular map to systematically determine the mechanisms of metabolic cross talk between members of the microbiota and define the role of these interactions in assembly of communities. We will study colonization and deconstruct mechanisms of community assembly using simple synesthetic microbial communities, gnotobiotics, and continuous flow cultivar systems. Our goal is to provide a detailed understanding of the spatial localization and molecular mechanisms of metabolic interactions in the microbiota during early life. Furthermore, we will define the molecular determinants that confer increased fitness for early life colonizing organisms. Together, this proposal will provide a framework for understanding the fundamental mechanisms of community assembly in infants and lead to the development of novel strategies for manipulating microbial communities in early life and during microbiota-associated disease.

项目总结

项目成果

Won't you be my neighbor? The importance of biogeography and nutrient niches in the gut.

你不愿意做我的邻居吗？

• DOI: 10.1016/j.chom.2022.05.009
• 发表时间: 2022
• 期刊: Cell host & microbe
• 影响因子: 30.3
• 作者: Abbas,Arwa;Zackular,JosephP
• 通讯作者: Zackular,JosephP

Clostridioides difficile and the Microbiota Early in Life.

艰难梭菌和生命早期的微生物群。

• DOI: 10.1093/jpids/piab063
• 发表时间: 2021
• 期刊: Journal of the Pediatric Infectious Diseases Society
• 影响因子: 3.2
• 作者: Semon,AlexaK;Keenan,Orlaith;Zackular,JosephP
• 通讯作者: Zackular,JosephP

Investigation of Microbial Cooperation via Imaging Mass Spectrometry Analysis of Bacterial Colonies Grown on Agar and in Tissue During Infection.

通过对感染过程中琼脂上和组织中生长的细菌菌落进行成像质谱分析来研究微生物合作。

• DOI: 10.3791/64200
• 发表时间: 2022
• 期刊: Journal of visualized experiments : JoVE
• 作者: Specker,JonathanT;Smith,AlexanderB;Keenan,Orlaith;Zackular,JosephP;Prentice,BooneM
• 通讯作者: Prentice,BooneM