The bacteria that reside within and upon us have a key role in maintaining our health. The intestinal microbiota provides a number of important functions for the host including processing and acquisition of nutrients, development of the immune system, modulation of bioavailable lipids, and serves as a barrier against pathogens. How the microbiota carries out these functions and how they can be manipulated in a diseased state to restore health is pooriy understood. The vast complexity of the gut microbial community has only recently begun to be addressed with the emergence of high-throughput sequencing technologies. However, most of the initial studies of the human microbiota have focused on identifying which organisms are present and not on functional aspects of microbial communities. In this project we will address a function of microbial communities of fundamental importance to the host: the ability to keep pathogens from colonizing and/or causing disease. Using bioreactor models and mice with a humanized intestinal microbiota we will begin to uncover the underiying ecological principles of how pathogen resistance is maintained within a community. We will also attempt to understand what types of disruption are sufficient to allow pathogens to invade the community and cause disease. To achieve these goals the following specific aims are proposed;
Specific Aim 1. Investigate how microbial community diversity affects the ability of diarrheal pathogens to become established within the community.
Specific Aim 2. Assess the effects of microbial community alterations on the ability of pathogens to cause disease in mice carrying a humanized micriobiota. The work proposed in these specific aims will address a key function of the intestinal microbiota using a combination of in vitro and in vivo approaches.

Public Health Relevance

Enteric infectious disease is a serious problems woridwide. Alterations in the bacteria we harbor inside our intestinal tract can create states in which pathogens can cause disease. The knowledge gained from the proposed work will provide a solid foundation for the development of therapeutics that target the microbiota or key metabolites that pathogens exploit when the intestinal microbiota is not functioning properiy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI090872-03
Application #
8381937
Study Section
Special Emphasis Panel (ZAI1-BLG-M)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$462,395
Indirect Cost
$184,550
Name
Michigan State University
Department
Type
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Spinler, Jennifer K; Auchtung, Jennifer; Brown, Aaron et al. (2017) Next-Generation Probiotics Targeting Clostridium difficile through Precursor-Directed Antimicrobial Biosynthesis. Infect Immun 85:
Brooks, Phillip T; Brakel, Kelsey A; Bell, Julia A et al. (2017) Transplanted human fecal microbiota enhanced Guillain Barré syndrome autoantibody responses after Campylobacter jejuni infection in C57BL/6 mice. Microbiome 5:92
Mukherjee, Sanjana; Mosci, Rebekah E; Anderson, Chase M et al. (2017) Antimicrobial Drug-Resistant Shiga Toxin-Producing Escherichia coli Infections, Michigan, USA. Emerg Infect Dis 23:1609-1611
Cha, W; Henderson, T; Collins, J et al. (2016) Factors associated with increasing campylobacteriosis incidence in Michigan, 2004-2013. Epidemiol Infect 144:3316-3325
Cha, Wonhee; Mosci, Rebekah; Wengert, Samantha L et al. (2016) Antimicrobial Susceptibility Profiles of Human Campylobacter jejuni Isolates and Association with Phylogenetic Lineages. Front Microbiol 7:589
Boughner, Lisa A; Singh, Pallavi (2016) Microbial Ecology: Where are we now? Postdoc J 4:3-17
Sloup, Rudolph E; Cieza, Roberto J; Needle, David B et al. (2016) Polysorbates prevent biofilm formation and pathogenesis of Escherichia coli O104:H4. Biofouling 32:1131-1140
Venegas-Vargas, Cristina; Henderson, Scott; Khare, Akanksha et al. (2016) Factors Associated with Shiga Toxin-Producing Escherichia coli Shedding by Dairy and Beef Cattle. Appl Environ Microbiol 82:5049-56
Tseng, M; Sha, Q; Rudrik, J T et al. (2016) Increasing incidence of non-O157 Shiga toxin-producing Escherichia coli (STEC) in Michigan and association with clinical illness. Epidemiol Infect 144:1394-405
Flies, Andrew S; Mansfield, Linda S; Flies, Emily J et al. (2016) Socioecological predictors of immune defences in wild spotted hyenas. Funct Ecol 30:1549-1557

Showing the most recent 10 out of 61 publications