The impact of probiotic bacteria on intestinal barrier function

Abstract

It has been widely reported that probiotics have a variety of health benefits, however, the underlining mechanisms for these are mainly unknown. This KESS project was a collaboration with Cultech Ltd., a company that produces such a probiotic formulation, called Lab4, which has been shown in several clinical trials to have such benefits for gut health. Our hypothesis was that the health benefits reported, are related to augmentation of epithelial barrier integrity. To evaluate this, we established in vitro models of varying complexity to assess molecular responses of probiotic application to a mature epithelium. My results revealed, that conditioned medium (metabolites) from Lab4 improved barrier integrity and importantly, that this had a protective effect when a subsequent inflammatory stimulus (IL-22) was applied. Furthermore, I found, that inclusion of mucus producing cells altered the epithelial responses to the inflammatory challenge. The main probiotic-mediated change observed, was in the pattern of activation of the MAPK signalling pathway, which is known to control epithelial proliferation. Based on our findings we propose, that short-chain fatty acids (SCFA) are a key active constituent of Lab4 probiotic conditioned media, and that these modulate ERK1/2 activation, and thereby modulate the responses of the epithelial lining and ultimately control barrier integrity. These novel findings provide important insights on actions in the host, driven by probiotic strains of Bifidobacterium and Lactobacillus on a mechanistic level, that significantly advance our current understanding, and may explain how probiotics mediate their health benefits