Enteral and parenteral nutrition distinctively modulate intestinal permeability and T cell function in vitro

Abstract

Nutritional support is an established element of therapy for various indications. However, its impact on the mucosal barrier function is not well understood. We investigated the influence of EN and PN on intestinal epithelial cells and peripheral blood (PBMC) and lamina propria mononuclear cells (LPMC), all of which are involved in the mucosal defense against bacterial translocation and systemic inflammation. Integrity of epithelial cells was measured as transepithelial electrical resistance (TER) of confluent Caco-2 monolayers in the presence of 1% EN, PN and a parenteral amino acid mixture (AM). To determine wound healing capacities, an established migration model with IEC-6 cells was used. Furthermore, we investigated apoptosis, cell activation, proliferation and cytokine secretion of Caco-2, HT29 and of stimulated PBMC and LPMC cultured with or without 1 and 5% EN, AM or PN. We demonstrated that EN, AM and PN promoted the integrity of the epithelial monolayer and reconstituted epithelial cell continuity TGF-beta-dependently and -independently. Interestingly, only PN induced apoptosis and decreased the mitochondrial membrane potential. The activation status of PBMC was significantly reduced by EN and AM. Specifically, EN leads to an increased apoptosis rate, inhibited cell cycle progression and increased pro-inflammatory cytokine secretion. Both EN and PN reduced the activation status and the release of pro- and anti-inflammatory cytokines. Our study provides evidence that by promoting wound healing and regulating T cell function, EN, AM, and PN potently interact with the intestinal barrier and immune system, thus justifying its use in diseases accompanied by impaired mucosal barrier function.