Colorado PROFILES, The Colorado Clinical and Translational Sciences Institute (CCTSI)
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Esophageal Haemophilus influenzae contribution to Eosinophilic Esophagitis


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? DESCRIPTION (provided by applicant): Eosinophilic Esophagitis (EoE) is a chronic inflammatory disease that affects around 150,000 people per year in the US and incurs an estimated $100,000,000 in endoscopy costs alone each year. Patients with EoE suffer from severely reduced quality of life due to dysphagia, food impaction, and vomiting. Th2 mediated inflammation in response to food and aeroallergen has been proposed as one pathogenic mechanism. However, the underlying triggers and mechanisms of inflammation in EoE are incompletely understood thus preventing improvements in standard of care treatments consisting of topical steroids and/or diet restriction. Alterations in the gastrointestinal microbiome have been associated with the pathogenesis of a number of other gastrointestinal diseases. Moreover, with the recent recognition of an altered microbiome in other eosinophil associated diseases such as asthma and eczema, we have prospectively measured the esophageal microbiome from patients with EoE and compared them to healthy controls. Using our minimally- invasive device, the esophageal string test we now have identified that non typable Haemophilus influenzae (H. influenzae) is significantly increased in the esophagus of patients with EoE. The mechanistic role of interactions between H. influenzae, the Th2 micromilieu and esophageal epithelial cells in promoting inflammation has not been determined. We hypothesize that H. influenzae increases the release of eosinophilic cytokines and chemokines from esophageal epithelial cells in the EoE micromilieu. The overall goal of this proposal is to determine the mechanisms through which H. influenzae activates esophageal epithelial cells leading to the EoE microenvironment. The following aims will test these hypotheses. Aim 1: Determine the microbiome in untreated and treated EoE subjects as compared to normal controls and subjects with Gastroesophageal Reflux Disease (GERD). Aim 2: Determine the inflammatory molecules increased by H. influenzae in the EoE micromilieu.
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R21AI119391

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Collapse start date
2016-08-20
Collapse end date
2020-07-31

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