The Protective Influence of Chondroitin Sulfate, a Component of Human Milk, on Intestinal Bacterial Invasion and Translocation.

Abstract

Human milk is known to be protective against necrotizing enterocolitis, a devastating intestinal inflammatory disease affecting the preterm population. Although the pathogenesis of necrotizing enterocolitis is yet to be solidified, intestinal integrity dysfunction, bacterial invasion and/or translocation, and inflammation may play important roles. Glycosaminoglycans, compounds naturally prevalent in both human milk and the intestine, are thought to be anti-inflammatory and capable of altering bacterial interactions within the gut. In this study, we aimed to evaluate the potential of chondroitin sulfate, the most prominent class of glycosaminoglycans in human milk, to protect against bacterial infection in an intestinal in vitro model. T84 cell monolayers were treated with chondroitin sulfate and cell viability was assessed across a number of doses. Monolayers were then pretreated with chondroitin sulfate and subsequently challenged with E. coli invasion and translocation to evaluate any protective role of the compound against infection. Tight junction barrier function was assessed by transepithelial electrical resistance, and cytokine levels were evaluated. Chondroitin sulfate at any dose up to 750 μg/ml was not associated with any statistically significant decrease in cell viability. Additionally, chondroitin sulfate at 750 μg/ml was associated with a 75% decrease in both bacterial invasion and translocation compared to control. These data suggest chondroitin sulfate may protect against bacterial infection through a reduction in both invasion and translocation, importantly without attendant reduction in cell viability.