The guts of all animals, including humans, contain vast numbers of bacteria that appear to live in harmony with their hosts. To advance knowledge of how animals and humans benefit from their resident bacteria, the ways that bacteria communicate with their hosts must be understood. This project identifies the molecules, called metabolites that are produced when bacteria digest food in the host's gut. Bacterial metabolites can be absorbed into the host body where they are used for nourishment, and they also provide a crucial communication link between bacteria and the host's own cells. Besides using the host's diet, some bacteria produce metabolites by breaking down molecules that are part of the host's gut, which is normally a healthy process but not well understood. To determine which metabolites in the host's body come from bacteria breaking down food vs. the gut molecules, researchers will use ground squirrels that eat during summer and then stop eating during their winter hibernation season. Researchers will sequence the DNA of gut bacteria to reveal how their genetic makeup relates to production of different metabolites that appear in the body of summer and winter squirrels, including those produced from food or from host molecules. Project findings will increase knowledge of how animals and their bacteria communicate and influence each other during altered dietary conditions. The project will develop educational modules for middle and high school students to teach concepts about the role of gut microbes in nutrition and health, using hibernation as an engaging and unifying theme.

A challenge in understanding host-gut microbe relationships is identifying metabolites produced by the gut microbiota that are incorporated into the host metabolome, thus potentially influencing host physiology. Bacterial-derived metabolites originate from degradation of dietary substrates or from endogenous compounds produced by the host. This project uses hibernation, in which the host animal ceases feeding for long periods each year, coupled with experimental microbiota depletion to identify bacterial metabolites in host tissues produced from dietary vs. host-derived substrates. The bacterial metagenome, its metabolic output (metabolome) and the host's metabolome will be assessed in squirrels feeding in summer, fasted in hibernation and refed in spring, some treated with antibiotics to deplete the microbiota. Microbiota capacity to degrade a complex plant glycan and a simple sugar will be assessed through breath responses to orally-administered 13C-labeled substrates and targeted and untargeted metabolomics analyses of microbiota and host tissue. Bacterial contribution to protein sparing during hibernation is measured using targeted metabolomic analysis of 15N-labeled proteins incorporated after injection of 13C,15N-labeled urea. Bioinformatic tools will be used to construct a system-based analysis that integrates the bacterial metagenome and metabolome features of the hibernator host and its seasonally changing microbiota. Results of the project will for the first time integrate the gut microbiome into hibernation biology and produce new knowledge that can be applied to other animal-microbial symbioses in which food resources vary over time.

National Science Foundation (NSF)
Division of Integrative Organismal Systems (IOS)
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Mamta Rawat
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University of Wisconsin Madison
United States
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