Physical Structure and Inter-Species Interactions in Gut Microbial Communities

肠道微生物群落的物理结构和种间相互作用

• 批准号: 2310570
• 负责人: Raghuveer Parthasarathy
• 金额: $ 60.11万
• 依托单位: University of Oregon Eugene
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2310570&HistoricalAwards=false
• 关键词: Physical; Structure; Inter; Species; Interactions

Resident within each of our intestines are trillions of microbes representing hundreds of species. These microorganisms compete, cooperate, and interact with each other and with our human cells and organs, and in doing so influence both normal physiological processes and a wide range of challenging diseases. Our understanding of how intestinal ecosystems are structured, how structure influences function, and how structure and composition can be altered remain minimal, in part because these ecosystems are not easily recapitulated in in “petri dish” studies. The gut microbiome operates under strong physical constraints. Species coexist at high densities, forcing them close to boundaries as well as competitors, and are subject to vigorous flows as the gut transports and processes food. Understanding the structure of the gut microbiome therefore requires observation and quantitative characterization of real intestinal environments, motivating this award. The investigators’ labs have pioneered the use of three-dimensional microscopy of larval zebrafish to gain insights into physical aspects of the gut microbiome. Zebrafish share many physiological similarities with humans and other vertebrates, making them an excellent animal model. At young ages they are quite transparent, and the recently developed technique of “light sheet fluorescence microscopy” enables fast, three-dimensional imaging over fields of view spanning the entire intestine, with resolution capable of discerning individual gut bacteria. Past work has shown that many gut bacterial species form aggregates: three-dimensional colonies with populations ranging from a few cells to tens of thousands of members. These observations raise fundamental questions about the nature and consequences of intestinal aggregation that this project aims to answer. First: Are there structural signatures of interactions among bacterial species? In zebrafish prepared such that only a single bacterial species is resident in the gut, the investigators have shown that the statistical distribution of aggregate sizes reflects physical processes of coalescence, fragmentation, and intestinal transport. In addition, multi-species communities coexist to a much greater degree than would be expected, for reasons that remain mysterious. The investigators suspect that the characteristics of aggregates, for example how aggregates of competing species are situated in the intestinal landscape and how species alter other species’ aggregation behaviors, can explain gut bacterial community structure. Second: Can aggregation state predict susceptibility to invasion? Intestinal microbes are constantly visited by new bacteria, but the reasons for resistance or susceptibility to invaders are poorly understood. This project focuses on a bacterial invader capable of altering the physical environment of the gut, namely a strain that enhances the strength of gut mechanical contractions. The investigators hypothesize that aggregation state is a major factor in invasion susceptibility, as large aggregates are readily transported and expelled by the contractions of the gut. This award involves the construction of intestinal communities in zebrafish composed of different numbers and types of species, linking observations of microbiome organization with invasion outcomes. In addition, experiments that select for invasion-resistant communities may be of particular importance for generating intestinal resilience in other animal species, including humans.In addition to the experiments and analyses described above, the investigators will design educational activities that use microbiome data to illustrate the intersection between biological imaging and computational analysis. These will be implemented in a day camp that targets low socio-economic status high school students.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.

我们的每个肠内的居民是几万亿微生物，这些微生物互相竞争。 “培养皿”的研究，肠道微生物组的慢速限制。激励人物的实验室具有幼体斑马鱼的开创性托雷维显微镜，使肠道微贝的phy曲线变成了相当透明的年龄跨越整个肠子的野生动物，可以辨别单个肠道的肠道肠道。旨在回答细菌物种之间的相互作用的目的。对于比聚集体的赛车的竞争方式，要比肠道的聚集体在肠道景观中如何改变其他细菌群体，但对肠道的群体结构可以解释新细菌的结构。被忽略的。物种类型，将微生物的观测与入侵结果联系在一起。 usrob iome数据的设计教育激活是为了说明交集的序列成像和计算分析。和更广泛的影响审查标准。