Mechanisms Underlying the Therapeutic Efficacy of Exclusive Enteral Nutrition in Crohn's Disease
Abstract
Crohns disease (CD) is an inflammatory bowel disease (IBD), characterized by recurrent transmural inflammation in the colon or/and ileum. Exclusive enteral nutrition (EEN), involving oral or nasogastric tube feeding of a complete liquid diet with exclusion of normal foods, is a safe and effective treatment for active CD. However, what accounts for the benefits of EEN in CD are not clear. Our project aims to investigate the mechanisms of the benefits of EEN. We hypothesize that: 1)Transmural inflammation in CD causes mechanical stress (MS) in the inflammation and pre-inflammation sites, and the MS induces expression of certain mechanosensitive genes to contribute to the development of inflammation and bowel dysfunctions; 2) EEN treatment is beneficial in CD by preventing MS and blocking the effects of MS-induced gene expression. Accordingly, our Specific Aims are: 1) To determine if MS plays a role in the development of CD by evaluating the effects of EEN on mechanosensitive gene expression, inflammation and bowel dysfunction; 2) To investigate the mechanisms underlying the beneficial effect of EEN on gut inflammation in CD; 3) To investigate the mechanisms underlying the beneficial effect of EEN on bowel dysfunctions, especially motility dysfunction. So far, we have almost completed the study in Aim 1. We found that intracolonic instillation of TNBS induces a localized transmural inflammation (as in CD) in the distal colon, which is associated with mechanical tension in the local inflammation site and lumen distention in the bowel prior to inflammation. These changes represent significant MS in the colon, and induce marked induction of certain pro-inflammatory mediators such as osteopontin (OPN) and cyclo-oxygenase-2 (COX-2) in the inflammation and pre-inflammation sites, which contribute significantly to the development of inflammation and bowel symptoms. EEN treatment decreases feces production, and prevents inflammation-associated MS, and dramatically attenuate
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2021
- Accession Number
- AD1164107
Entities
People
- Xuan-Zheng Shi
Organizations
- University of Texas Medical Branch