Short Chain Fatty Acids and Intestinal Barrier Function

Project Details

Description

[unreadable] DESCRIPTION (provided by applicant): Prematurity, enteral formula feeding, and bacterial colonization are three major risk factors for neonatal necrotizing enterocolitis (NEC). However, the etiology and pathogenesis of NEC remain unclear. Acetic acid, propionic acid and butyric acid are short chain fatty acids (SCFAs), which are produced mainly in the colon by bacterial fermentation of undigested carbohydrates. Although luminal production of modest quantities of SCFAs is essential for normal colonic mucosal function, excessive production/accumulation of SCFAs may arise in premature infants due to increased luminal carbohydrate malabsorption and poor gastrointestinal motility, and may have deleterious effects on mucosal integrity. Data from our preliminary study and other published studies stongly suggest that the effect of SCFAs on the intestinal mucosal barrier is paradoxical, i.e. while low concentrations of SCFAs may be beneficial in promoting mucosal barrier function, excessive luminal SCFAs may cause intestinal injury by disrupting the mucosal barrier. To further examine the effects of SCFA on the intestinal epithelial barrier function, we will use an in vitro model of intestinal epithelial barrier with Caco-2 cells grown in a trans-well system and examine whether tight junction associated proteins are involved in the butyrate regulation of intestinal mucosal barrier function. We hypothesize that butyrate regulates the intestinal barrier function via, at least in part, the regulation of tight junction associated proteins. The specific aim of this study is to examine the molecular mechanisms underlying the effects of butyrate on the intestinal barrier function in a well characterized model of intestinal epithelial barrier by using newer available molecular techniques. The results of this study may help us to further understand the pathogenesis of NEC and lead to the development of novel prevention strategies and treatment methods. [unreadable] [unreadable] [unreadable]
StatusFinished
Effective start/end date1/03/0628/02/09

Funding

  • National Institute of Child Health and Human Development: $82,292.00
  • National Institute of Child Health and Human Development: $84,750.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.