Biocompatible Nanocomposite Tailored to Endure the Gastric Niche Renders Effective in Vitro Elimination of Intestinal Pathogenic Bacteria and Supports Adhesion by Beneficial Bacteria.

Abstract

Bacteriocins produced by lactic acid bacteria (LAB) are potent therapeutic arsenals for targeting gastrointestinal pathogens and a promising alternative to antibiotics, because of their selective activity and reduced propensity to trigger collateral damage to the beneficial gut microbes. However, proteolytic inactivation in the gastric niche renders bacteriocins ineffective. The present study addresses this challenge and demonstrates that a biocompatible milk protein fraction can be leveraged to generate a robust nanocargo, which renders protection from proteolysis in the gastric milieu and facilitates delivery of the encapsulated bacteriocin pediocin. In a simulated gastric transit experiment, pediocin-loaded milk protein nanocomposite (Ped-MNC) could render a 3.0 log reduction in the viability of model gastrointestinal pathogens. Ped-MNC is nontoxic to cultured human intestinal cells (HT-29 cells) and effectively abrogates pathogenic bacteria adhering onto intestinal cells. In a combinatorial regimen, Ped-MNC and the beneficial LAB Lactobacillus plantarum DF9 could substantially reduce the levels of the pathogen Enterococcus faecalis MTCC 439 adhering onto HT-29 cells and interestingly the nanocomposite does not hinder adhesion of intestinal cells by the beneficial LAB. The developed nanocomposite holds promise as a niche specific therapeutic for selective mitigation of intestinal pathogens.