The gut microbiota contributes to the protein nutrition of humans and other animals. This study will use the model insect Drosophila melanogaster to determine how hosts interact physiologically and genetically with their gut microbes to maximize protein nutrition as well as overall health and fitness. The basis of this proposal is that the nutritional physiology and symbiosis of animals are interdependent, such that animal protein nutrition can only be understood fully when considered as a symbiotic system. Furthermore, this symbiotic system is highly dynamic: perturbation to the microbiota or diet can have major impact on the protein nutrition, acting through interactions between host nutritional physiology and the composition/function of the microbiota, with profound impacts on the health of the host. Drosophila is particularly amenable to this study because it is highly homologous to humans in its nutritional requirements, but has the experimental advantage of possessing a simple gut microbiota that can be manipulated easily. Drosophila can also be reared on a variety of experimental diets, allowing tests for the effect of diet composition, mimicking dietary behavioral modification in humans. The proposed study will measure the physiological consequences of dietary and symbiotic manipulation on Drosophila on protein nutrition and overall health and fitness. It will test the hypothesis that host genetic variation in the assimilation and allocation of protein precursors underlies variation in dependence on symbiotic associations for maximal health, and will use genomic resources and systems analyses to define the expression networks that underpin symbioses with different impacts on host protein nutrition. This research will achieve the first understanding of the mechanisms underlying natural variation in the significance of the gut symbiosis to host protein nutrition, with direct relevance to understanding human dietary and nutritional conditions and their impacts on health.

Public Health Relevance

Symbiotic bacteria in the gut play an important role in protein nutrition, and therefore to the overall health and fitness of humans and other animal hosts. The proposed study will investigate the physiological mechanisms by which gut microbes impact host protein metabolism, will quantify host genetic variation for interactions with gut microbes, and will construct a synthetic gene expression network to describe the symbiotic system. The work will contribute to understanding the dietary and genetic factors underpinning clinical metabolic and nutritional conditions, and the impacts of gut symbiosis on health.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM095372-04
Application #
8598904
Study Section
Special Emphasis Panel (ZGM1-GDB-2 (MC))
Program Officer
Sledjeski, Darren D
Project Start
2011-01-01
Project End
2014-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
4
Fiscal Year
2014
Total Cost
$320,773
Indirect Cost
$112,479
Name
Cornell University
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Douglas, Angela E (2014) Symbiosis as a general principle in eukaryotic evolution. Cold Spring Harb Perspect Biol 6:
Wong, Adam C-N; Dobson, Adam J; Douglas, Angela E (2014) Gut microbiota dictates the metabolic response of Drosophila to diet. J Exp Biol 217:1894-901
Chaston, John M; Newell, Peter D; Douglas, Angela E (2014) Metagenome-wide association of microbial determinants of host phenotype in Drosophila melanogaster. MBio 5:e01631-14
Newell, Peter D; Douglas, Angela E (2014) Interspecies interactions determine the impact of the gut microbiota on nutrient allocation in Drosophila melanogaster. Appl Environ Microbiol 80:788-96
Wong, Adam C-N; Chaston, John M; Douglas, Angela E (2013) The inconstant gut microbiota of Drosophila species revealed by 16S rRNA gene analysis. ISME J 7:1922-32
Scott, Jeffrey G; Michel, Kristin; Bartholomay, Lyric C et al. (2013) Towards the elements of successful insect RNAi. J Insect Physiol 59:1212-21
Douglas, Angela E (2013) Microbial brokers of insect-plant interactions revisited. J Chem Ecol 39:952-61
Karasov, William H; Douglas, Angela E (2013) Comparative digestive physiology. Compr Physiol 3:741-83
Ridley, Emma V; Wong, Adam C N; Douglas, Angela E (2013) Microbe-dependent and nonspecific effects of procedures to eliminate the resident microbiota from Drosophila melanogaster. Appl Environ Microbiol 79:3209-14
Douglas, Angela E; Dobson, Adam J (2013) New synthesis: animal communication mediated by microbes: fact or fantasy? J Chem Ecol 39:1149

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