Oligosaccharides: A promising new approach for minimizing the pathological effects of deoxynivalenol on the intestinal tract

INTRODUCTION: Non-digestible oligosaccharides (NDO) have demonstrated to not only exert beneficial effects on the composition and activity of the intestinal microflora in the gastrointestinal tract, but these compounds have also been associated with immune-modulating effects in the intestine. One of the most prominent sources of oligosaccharides is milk and it is established that particularly collostrial oligosaccharides modulate the enteric immune response. Mycotoxin exposure, a worldwide problem in the livestock industry, causing next to acute intoxication, immunosuppression and gastro-intestinal illness. Specific lesions observed at the intestinal level include induction and promotion of inflammatory reactions and an increased susceptibility to intestinal infections, losses in productivity and reduced weight gain. One of the most prevalent mycotoxins in European cereals and cereal products, important sources of energy and protein for all classes of farmed livestock, is the trichothecene deoxynivalenol (DON). The aim of this study is to investigate the effect of DON on epithelial integrity and to test the hypothesis whether specific oligosaccharides can mitigate the DON related pathological effects at the intestinal epithelial layer. MATERIALS AND METHODS: Using the human epithelial intestinal cell line Caco2 in a transwell system as an in vitro model, we studied the effect of DON on transepithelial electrical resistance (TEER), lucifer yellow (LY) permeability, tight junction protein expression and IL-8 release. In this study the ability of NDO, to inhibit the DONrelated effects was investigated. RESULTS: The TEER of Caco-2 cells was dose-dependently reduced following DON exposure and a significant increase in LY permeability was observed after 24 h. These alterations of the intestinal barrier function were associated with an increase in mRNA expression of occludin, claudin1, claudin3, claudin4, ZO- 1 and ZO-2 after 6 h incubation with DON and an increase in IL- 8 production after 24 h. Interestingly, after 24 h incubation with NDO the DON-induced impairment of the intestinal barrier was mitigated and the increased IL-8 levels in the apical as well as the basolateral chamber induced by DON were significantly decreased. Furthermore, the claudin4 mRNA expression is further increased after incubation with NDO. CONCLUSIONS: We conclude that NDO can restore the DON-induced effect on epithelial barrier function and exert an anti-inflammatory effect by reducing IL-8 levels. The results suggested that the intake of galacto-oligosaccharides can reduce the direct effects of DON on the intestinal epithelial integrity. Taken together, the dietary application of specific oligosaccharides to mitigate pathological effects of the fungal toxin DON related to intestinal epithelial cells offers a promising concept for mycotoxin exposure intervention.