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

Abstract

Background: 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. Research aim: 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. Methods: 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. Results: 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. Conclusions: 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.

Antiviral Properties of Human Milk

“…Newburg and colleagues showed CS can inhibit the binding of HIV’s glycoprotein, gp120 to the host cell CD4 receptor [ 115 ]. This study is consistent with another which showed that CS in isolation can be protective to an intestinal in vitro system [ 136 ].…”

Effects of oropharyngeal administration of colostrum on the incidence of necrotizing enterocolitis, late-onset sepsis, and death in preterm infants: a meta-analysis of RCTs

“…The key results of previous studies in this field need to be discussed. Some studies found that colostrum was effective in reducing the rate of NEC, revealing its effect in building up immunity [11,[39][40][41][42]. Term babies could suck their mothers' nipples to obtain breast milk and their immunity would be triggered through the first bite with colostrum being served as stimulator [43,44].…”

The Role of Glycosaminoglycans in Protection from Neonatal Necrotizing Enterocolitis: A Narrative Review

“…A dose-dependent reduction in bacterial invasion occurred with CS (M ± SEM), with 750 µg/mL showing significantly lower bacterial invasion compared to control (** p = 0.0071; eta-squared = 0.0944); (b) CS at 750 µg/mL was significantly protective by the third hour of inoculation (M ± SEM, ** p = 0.0018). (Reprinted with permission of authors and SAGE Publishing [194]).…”

“…Our group has also directly interrogated the ability of CS, the most common GAG in HM [146], to limit both bacterial invasion ( Figure 3a) and translocation ( Figure 3b) in T84 colonocyte monolayers, an in vitro model of the intestinal epithelium [194]. CS, at a concentration of 750 µg/mL given prophylactically for 48 h prior to bacterial challenge, reduces invasion and translocation of SCB34 Escherichia coli, an invasive, multi-drug resistant bacterial strain isolated from a neonatal early-onset sepsis case [195], by 75% compared to control.…”