VSL#3 probiotics regulate the intestinal epithelial barrier in�vivo and in vitro via the p38 and ERK signaling pathways

Abstract

Abstract. Probiotics can play a role in enhancing intestinal barrier function. However, the underlying mechanisms are not fully understood. The aim of this study was to examine the effects of VSL#3 probiotics on colonic epithelium permeability, tight junction protein expression and MAPKs signaling pathways in vivo and in vitro. In vivo, acute colitis was induced by administration of 3.5% dextran sodium sulfate for 7 days. Rats in two groups were treated with either 15 mg VSL#3 or placebo via a gastric tube once daily after induction of colitis. Tight junction protein expression and the MAPKs signaling pathways were studied by immunohistochemistry and immunoblotting. In vitro, HT-29 cells were exposed to TNF-α for up to 48 h with or without pre-treatment with a p38 MAPK inhibitor, an ERK inhibitor or a JNK inhibitor. Then tight junction proteins and the phosphorylation of MAPKs were examined in the presence or absence of VSL#3. In vivo, VSL#3 probiotics significantly ameliorated the disease activity index from Day 4 onward. In acute colitis rats, decreased expression of the tight junction proteins were observed, whereas VSL#3 therapy prevented these changes and increased the expression of phosphorylated p38 (P-p38), and of phosphorylated ERK (P-ERK). In vitro, tight junction proteins, P-p38 and P-ERK in the VSL#3 group were significantly higher than in the control and TNF-α groups. The p38 MAPK inhibitor and the ERK inhibitor could effectively prevent this effect. VSL#3 probiotics protected the epithelial barrier and increased the tight junction protein expression in vivo and in vitro by activating the p38 and ERK signaling pathways.

IL-33 Signaling Protects from Murine Oxazolone Colitis by Supporting Intestinal Epithelial Function

“…41 For example, TGF-β increases T84 barrier function in vitro , and a probiotic mixture increases intestinal barrier function in vivo through an ERK1/2-dependent mechanism. 42,43 In line with our in vitro results, we observed that ST2 −/− mice exhibit impaired colon barrier function as evidenced by decreased TER and increased macromolecule permeability compared to WT mice. These data support a homeostatic role for IL-33 in maintaining epithelial barrier integrity.…”

Organoids, organs-on-chips and other systems, and microbiota

“…Additionally, this system allows the study of physiological gut functions in the presence of relevant cues and interactions with the microflora. Caco-2 cells have been effectively co-cultured with a naturally occurring intestinal microbe, Lactobacillus rhamnosus GG (LGG), at the luminal surface which improved intestinal barrier function [43], which has been previously reported with probiotic bacteria strains in humans [128]. Moreover, differentiated intestinal epithelium supported the growth of naturally occurring microbiota for more than 2 weeks, which is in contrast with Transwell and organoid cultures where cell viability is often lost within a few hours [12,14,43].…”

Gut Microbiota: A Key Modulator of Intestinal Healing in Inflammatory Bowel Disease

“…The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells Furthermore, it was shown that VSL#3 improves intestinal barrier by stimulating the expression of ZO-1, and occludin, and by decreasing claudin-2. Probiotic bacteria are able to regulate intestinal epithelial permeability in experimental ileitis by a TNF-dependent mechanism and interact with IECS, activating the p38 MAPK and ERK signaling pathways [63]. …”