Year of Publication

2011

Degree Name

Doctor of Philosophy (PhD)

Document Type

Dissertation

College

Medicine

Department

Microbiology, Immunology, and Molecular Genetics

First Advisor

Dr. Alan Kaplan

Abstract

Inflammatory Bowel Diseases, Crohn's Disease and Ulcerative colitis, are idiopathic chronic conditions with multifactorial determinants. In general, terms, intestinal inflammation results from abnormal host-microbe interactions. Alterations in homeostasis involve host genetic factors, environmental cues and unique luminal microbial niches. We have examined the coordinated expressions of several molecular targets relevant to the mucosal immune system and identified signature biomarkers of IBD. Qualitative and quantitative changes in the composition of microbiota can be related to unique immuno-phenotypes. This in turn can have more systemic effects that involve energy metabolism. Adiponectin, an adipose tissue derived adipokine, can restore cellular ATP levels and fulfills innate immune functions. We have concluded that IBD might represent a state of adiponectin resistance relating to chronic inflammation and obesity status.

Lastly we hypothesized that activation of xenobiotic pathway (AHR-aryl hydrocarbon receptor) can further modulate host immune and metabolic responses, and thus contribute to IBD phenotypes. We found that IBD is associated with robust mucosal, aryl hydrocarbon receptor pathway and related to proinflammatory cytokine secretion. We conclude that IBD heterogeneity is reflected through distinct immunophenotypes. Furthermore, environmental cues that involve the AhR receptor and adipose tissue derived adiponectin are important regulators of the inflammatory process in IBD.

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