Niche Partitioning of Commensal Clostridia in the Gut

项目总结/摘要 考虑到肠道微生物群对人类健康和疾病的重要性，人们对确定如何 这些群落中的固有微生物聚集并发挥健康作用。生态演替 组成肠道微生物组的微生物从出生时就开始了，在整个过程中， 人类生活肠道微生物群的一个关键作用是分解我们现有饮食中的资源， 给我们提供生存所需的营养。这也维持了周围的其他微生物， 多样性和对环境扰动的适应能力。再加上肠道提供的丰富营养 在环境中，细菌使其营养获取库多样化的能力可以允许相关菌株 建立新的生态位并在社区中共存。因此，生态位分配在个别物种或 菌株可能有助于维持多样化的微生物群。选择模型的小生境划分 已经证明了肠道的微生物，如拟杆菌属，提供了关键的 关于有助于它们在肠道中组装的合作和竞争相互作用的知识。然而， 我们仍然缺乏关于肠道中许多流行物种的代谢策略的全面信息， 更不用说这些物种如何相互作用以维持特定的群落结构了。了解如何 在肠道中组装非模型微生物是重要的，因为许多靶向细菌的成功实施， 功能仍然依赖于他们周围的社区成员。在本提案中，我们的目标是描述 肠道梭菌的代谢作用，其代表肠道微生物群的普遍成员， 被低估了我们假设，类似于已知的更明确的肠道扩张， 种，梭菌物种之间的营养生态位分配是必不可少的，以维持其在肠道中的多样性。 我们将使用生物信息学和体外方法来1）表征基本（基因编码）和 实现（表达）选定梭菌物种使用的代谢策略; 2）确定这些如何 有助于它们在肠道中的组装。这些数据的结果提供了有关核心 功能，菌株异质性和微生物相互作用，与理解全面 人类肠道菌群的组装。这些数据提供了一个基础的机制研究， 肠道中的梭菌，如开发合理的细菌财团或基于饮食干预 这些基本特征。总的来说，这项建议为我们的独立国家提供了一条前进的道路。 该研究计划的重点是了解肠道梭菌在健康中的作用。

PROJECT SUMMARY/ABSTRACT Given the importance of the gut microbiota to human health and disease, there is great interest in defining how the indigenous microbes in these communities assemble and function in health. Ecological succession of the microbes that compose the gut microbiome begins at birth, with diversification of the community throughout human life. A key role for the gut microbiota is to break down resources from our available diet, which provides us with necessary nutrition to live. This also sustains other surrounding microbes, increasing microbiota diversity and resilience to environmental perturbation. In conjunction with the rich nutrients provided by the gut environment, the ability of a bacterium to diversify its nutrient acquisition repertoire can allow for related strains to establish new niches and coexist in a community. As such, niche partitioning among individual species or strains likely to contributes to maintenance of a diverse microbiota. Niche partitioning of select model commensal microbes of the gut, such as Bacteroides species, has been demonstrated, providing critical knowledge about the cooperative and competitive interactions that contribute to their assembly in the gut. Yet, we still lack comprehensive information about the metabolic strategies for many prevalent species in the gut, let alone how these species interact together to maintain a particular community structure. Understanding how non-model microbes assemble in the gut is important, as successful implementation of many targeted bacterial functions still rely on their surrounding community members. In this proposal, we aim to characterize the metabolic role of commensal Clostridia, which represent prevalent members of the gut microbiota that are under-characterized. We hypothesize that similar to what is known about more well-defined gut commensal species, nutrient niche partitioning among Clostridial species is essential to sustaining their diversity in the gut. We will use bioinformatic and in vitro methods to 1) characterize the fundamental (genonme-encoded) and realized (expressed) metabolic strategies used by select Clostridial species and 2) identify how these contribute to their assembly in the gut. Results from these data provide critical information about core functions, strain heterogeneity, and microbial interactions that are relevant to understanding comprehensive assembly of the human gut microbiota. These data provide a foundation for mechanistic studies surrounding commensal Clostridia in the gut, such as developing rational bacterial consortia or dietary interventions based on these fundamental characteristics. Overall, this proposal provides a path forward for our independent research program focused on understanding the role of commensal Clostridia in health.