Niche Partitioning of Commensal Clostridia in the Gut

项目总结/文摘

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.