A New Dimension in Modeling Irritable Bowel Syndrome (IBS) to Elucidate Novel Diagnostic Biomarkers and Microbiome Signatures A New Dimension in Modeling Irritable Bowel Syndrome (IBS) to Elucidate Novel Diagnostic Biomarkers and Microbiome Signatures Irritable Bowel Syndrome (IBS), the most commonly diagnosed gastrointestinal disorder in the U.S., affects up to 15% of people in North America and imposes a major health and economic burden . Despite its prevalence, the underlying cause(s) of IBS are poorly understood and the lack of predictive diagnostic biomarkers and effective treatment options makes diagnosing and managing this disorder a challenge for physicians and patients. Patients with IBS have temporal changes in their intestinal microbiome, vitamin D levels, and gene expression that have been implicated in pathogenesis; however, there is no data to support a link between these observed changes and causality for IBS. There is thus an urgent need for the development of biologically relevant models with which to dissect the cellular and molecular mechanisms of human IBS to provide predictive models to link discovery directly to the behavior of disease processes in vivo. We propose novel studies that provide the initial steps for optimization of our organotypic 3-D immunocompetent intestinal models for ex vivo generation of human IBS platforms to achieve our long-term goal to understand the relationship between gut microbiome, vitamin D levels and host gene expression and IBS symptoms. This will be accomplished by 1) populating the models with gut microbiota from fecal samples from IBS patients or healthy controls recruited from the Mayo Clinic, and 2) supplementing models with a range of vitamin D to mimic normal-deficient levels. Model viability, morphology, tight junction integrity, mucus production, proinflammatory cytokines, targeted gene expression, and 16S rDNA profiling of microbiota will be compared to patient-matched IBS and normal colonic tissue biopsies. Evidence linking intestinal microbiota to metabolic disorders including obesity and diabetes, suggests that inclusion of microbiota from diabetic and/or obese IBS patients in future studies may translate into novel approaches to prevent metabolic dysfunction and promote health.
|Effective start/end date||1/1/15 → 8/15/16|
- ASU: Mayo Seed Grant: $28,440.00
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