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Deciphering Interactions Between the Gut Microbiota and Host Immune System During Intestinal Inflammation
Interactions between the gut microbiota and the host immune system are very complex, ranging from commensalism and mutualism all the way to parasitism, depending on the organism and the status of the gut (i.e., healthy or inflamed). Although the majority of the bacterial members of the intestinal microbiota actively react with the immune system in a mutually beneficial relationship, the disruption of this equilibrium during inflammation allows for the emergence and enrichment of potentially pathogenic microbes (i.e. pathobionts) that are thought to contribute to the development of intestinal inflammation. In this work, we have shown that commensal gut-resident E. coli elicit strain-specific host immunological responses during acute gastrointestinal inflammation independent of their colonization levels in the gut. Amelioration of the intestinal inflammation induced by select commensal E. coli strains was achieved via neutralization of the pro-inflammatory cytokine interleukin-6. We also have investigated the causative role of adherent and invasive E. coli (AIEC), a newly-designated E. coli pathotype frequently isolated from intestinal biopsies of ileal Crohn’s disease patients, in the development of colitis. Utilizing a gnotobiotic mouse model devoid of Escherichia species, we have shown that AIEC directly contribute to the exacerbation of intestinal inflammation following chemical perturbation of the intestinal barrier. Moreover, we show that some of the in vitro phenotypes often used to describe AIEC strains predicts their ability to cause disease in vivo. Also in this work, we evaluated the ability of the prebiotic fiber galactooligosaccharide (GOS) to prevent the pro-inflammatory immune responses and colitis mediated by the intestinal pathogen Citrobacter rodentium. GOS feeding protected colonic tissues from the intestinal damage caused by C. rodentium independently of the well-described anti-adherence effects of GOS. Altogether, this work provides critical insight into the relationships between both resident and pathogenic Enterobacteriaceae and their host. Moreover, it also describes potential therapeutic interventions for treating the intestinal inflammation exacerbated or induced by these bacteria. Such knowledge, if applicable to humans, serves to strategically inform clinical diagnosis and therapeutics for patients suffering from the effects of gastrointestinal inflammation.
Kittana, Hatem Hassan Badr, "Deciphering Interactions Between the Gut Microbiota and Host Immune System During Intestinal Inflammation" (2018). ETD collection for University of Nebraska - Lincoln. AAI10792693.