Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. Modulating microbial communities for human health requires understanding the response of communities to invaders, but little is known about the mechanistic bases for community invasion. Our goal is to determine the genetic basis for invasion in the simple model, the gut community of Manduca sexta, and determine the impact of invasion on the meta-metabolome of the host-community complex. We will identify genes involved in invasion and then determine their role in competition and cooperation in the community and their impact on the metabolome to generate hypotheses about the role of signal molecules, antibiotics, and nutrients in community interactions. The project's innovation derives from the marriage of systems-level analysis of metabolite profiles with reductionist genetic analysis, the application of genetics to community-level phenotypes, quantification of microbial populations with luminescence imaging in live animals, and cutting edge chemical technology. The work has the potential to advance the field of microbial community ecology by providing a basis for deriving models about community behavior in the face of perturbation that may apply directly to human health.

Public Health Relevance

Microbial communities in the human gut have been linked with numerous diseases, from colon cancer to depression. Strategic approaches to health management necessitate manipulation of gut microbial communities. Establishing beneficial organisms, such as those in probiotics, requires invasion of a community; conversely, preventing invasion or overgrowth by other strains is essential to protecting the gut from pathogens. Little is known, however, about the mechanisms underlying invasion and resistance to invasion, making it challenging to manipulate communities in a directed manner. Understanding the nature of invasion and resistance to invasion in microbial communities is the focus of the work described here.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZGM1-GDB-2 (MC))
Program Officer
Sledjeski, Darren D
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Yale University
Schools of Arts and Sciences
New Haven
United States
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Fischer, Caleb N; Trautman, Eric P; Crawford, Jason M et al. (2017) Metabolite exchange between microbiome members produces compounds that influence Drosophila behavior. Elife 6:
Holt, Jonathan F; Kiedrowski, Megan R; Frank, Kristi L et al. (2015) Enterococcus faecalis 6-phosphogluconolactonase is required for both commensal and pathogenic interactions with Manduca sexta. Infect Immun 83:396-404
Blum, Jessamina E; Fischer, Caleb N; Miles, Jessica et al. (2013) Frequent replenishment sustains the beneficial microbiome of Drosophila melanogaster. MBio 4:e00860-13