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Dietary Modulation of Host-Microbe Interactions

Nickerson, Kourtney P
http://rave.ohiolink.edu/etdc/view?acc_num=case1386343814

Abstract Details

2014, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
Inflammatory bowel disease (IBD) is a chronic, debilitating intestinal disease affecting an estimated 1.3 million individuals in the United States alone, with worldwide incidence rapidly rising. Crohn’s Disease (CD), one subtype of IBD, is believed to arise in response to environmental priming resulting in inappropriate immune responses against commensal bacteria in a genetically susceptible individual. While the scientific community has made great progress in understanding the genetics and altered immune responses observed in CD patients, little is known about the environmental factors important in shaping disease. Sugar consumption and artificial sweeteners, as well as a “Western” diet, are environmental factors associated with onset of CD. We broadly hypothesized that diet was driving changes in bacterial adhesion promoting disease onset. We identified a polymer of glucose, maltodextrin (MDX), that modulates both bacterial interaction with the environment as well as cellular response to intracellular bacteria. MDX was identified as a phenotype-enhancing compound after panels of Escherichia coli species were subjected to an array of polysaccharides. Strains of adherent-invasive E. coli have been isolated from inflamed lesions of CD patients, while changes in spatial organization of the CD microbiome results in a bacterial biofilm adherent to the - 11 - intestine epithelium. E. coli species exhibit significant increases in bacterial adhesion after exposure to MDX and isolation of bacterial DNA from ileal CD patients had higher levels of the gene MalX, a bacterial gene require for metabolism of MDX. These data suggests the polysaccharide MDX can promote E. coli adhesion and may influence bacterial populations in CD patients. Genetic studies have identified clusters of CD-associated genes in antibacterial pathways; therefore we looked at the effect of cellular MDX in the context of intracellular bacterial clearance. Exposure of cells to MDX impaired intracellular Salmonella clearance through alterations in trafficking resulting in enhanced Salmonella viability. Similar results were observed in mice infected with Salmonella, 100-fold more viable bacteria recovered from the cecum of MDX fed mice. Our work identifies a role for the polysaccharide MDX in shaping host-microbial interactions which may be important for development of chronic disease states like CD.
Claudio Fiocchi, MD (Committee Chair)
Christine McDonald, PhD (Advisor)
Laura Nagy, PhD (Committee Member)
Xiaoxia Li, PhD (Committee Member)
Jean-Paul Achkar, MD (Committee Member)
126 p.
Microbiology

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Citations

  • Nickerson, K. P. (2014). Dietary Modulation of Host-Microbe Interactions [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1386343814

    APA Style (7th edition)

  • Nickerson, Kourtney. Dietary Modulation of Host-Microbe Interactions. 2014. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1386343814.

    MLA Style (8th edition)

  • Nickerson, Kourtney. "Dietary Modulation of Host-Microbe Interactions." Doctoral dissertation, Case Western Reserve University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1386343814

    Chicago Manual of Style (17th edition)

case1386343814
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© 2013, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.