Complex communities of microbes are intimately associated with the human body and integral to human health. Unlike pathogens that inflict damage as a consequence of their proliferation, communities of mutualistic microbes are essential for the normal functioning of the host. In the GI tract, microbes play critical roles in the maintenance of gut homeostasis, including competition against ingested pathogens ("colonization resistance"), detoxification of ingested compounds, maintenance of mucosal immunity and production of short-chain fatty acids - the preferred energy source of colonic enterocytes and a potent immunomodulatory signal. While co- evolution of microbes and their human host has led to a genetically diverse community of microbes in the gut, microenvironments in the host shape these communities. In this proposal we will focus on the influence of oxygen gradients on the structure and function of microbial communities. In the mammalian GI tract, oxygen diffuses into the lumen from the host, resulting in a microoxic zone where the low oxygen concentrations have the potential to impact both microbial communities and host cells. Long-held assumptions about the concentration of oxygen required to support respiration have been challenged recently by the finding that populations of E. coli grow and respire at oxygen concentrations less than 3 nM - more than 2 orders of magnitude below previous estimates. We propose to test the impact OF low oxygen environments on the structure and function of microbial communities in the mammalian GI tract. We will study the role of oxygen gradients in governing the structure and activity of microbial communities as we address the following specific aims: 1) Determine the diversity and abundance of bacteria in the human and murine intestinal microbiomes that have high-affinity cytochrome oxidases, and assess the competitive fitness of these microaerobes;2) Use in vitro spatially-structured microenvironments, with oxygen sensing elements, to assess the role of oxygen in determining the competitive fitness of microaerobes;and 3) Measure in vivo oxygen concentrations at the mucosal surface in germ free mice and mice colonized with or microbial communities. Additionally, we will determine if differences in strategies for dealing with oxygen gives a relative ecologic advantage to certain organisms. Understanding the role of oxygen in shaping the structure and function of microbial communities will advance our ability to build predictive models of interactions between the host and microbiota, not only in the GI tract, but anywhere on the body where biofilms create oxygen gradients.

Public Health Relevance

Understanding the role of oxygen in shaping the structure and function of microbial communities in the intestinal mucosa will advance our ability to build predictive models of interactions between the host and microbiome. Such an understanding will provide information important not only in the GI tract, but anywhere in the body where microbial biofilms create oxygen gradients.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM099549-02
Application #
8633468
Study Section
Special Emphasis Panel (ZGM1-GDB-2 (MC))
Program Officer
Sledjeski, Darren D
Project Start
2013-03-07
Project End
2017-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$263,522
Indirect Cost
$63,694
Name
University of Michigan Ann Arbor
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109