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 #
5R01GM095372-03
Application #
8400889
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
2013-01-01
Budget End
2013-12-31
Support Year
3
Fiscal Year
2013
Total Cost
$353,674
Indirect Cost
$124,016
Name
Cornell University
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Dobson, Adam J; Chaston, John M; Douglas, Angela E (2016) The Drosophila transcriptional network is structured by microbiota. BMC Genomics 17:975
Chaston, John M; Dobson, Adam J; Newell, Peter D et al. (2015) Host Genetic Control of the Microbiota Mediates the Drosophila Nutritional Phenotype. Appl Environ Microbiol 82:671-9
Huang, Jia-Hsin; Jing, Xiangfeng; Douglas, Angela E (2015) The multi-tasking gut epithelium of insects. Insect Biochem Mol Biol 67:15-20
Douglas, Angela E (2015) Multiorganismal insects: diversity and function of resident microorganisms. Annu Rev Entomol 60:17-34
Dobson, Adam J; Chaston, John M; Newell, Peter D et al. (2015) Host genetic determinants of microbiota-dependent nutrition revealed by genome-wide analysis of Drosophila melanogaster. Nat Commun 6:6312
Wong, Adam C-N; Luo, Yuan; Jing, Xiangfeng et al. (2015) The Host as the Driver of the Microbiota in the Gut and External Environment of Drosophila melanogaster. Appl Environ Microbiol 81:6232-40
Sams, Aaron J; Hawks, John; Keinan, Alon (2015) The utility of ancient human DNA for improving allele age estimates, with implications for demographic models and tests of natural selection. J Hum Evol 79:64-72
Huang, Jia-Hsin; Douglas, Angela E (2015) Consumption of dietary sugar by gut bacteria determines Drosophila lipid content. Biol Lett 11:20150469
Douglas, Angela E (2014) The molecular basis of bacterial-insect symbiosis. J Mol Biol 426:3830-7
Douglas, Angela E (2014) Symbiosis as a general principle in eukaryotic evolution. Cold Spring Harb Perspect Biol 6:

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