Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines

Abstract

Background/Aims: Recent studies have demonstrated that the manipulation of the gut microbiome represents a promising treatment for inflammatory bowel disease (IBD). We previously identified micro integral membrane protein (MIMP) as the smallest domain of surface layer protein from Lactobacillus Plantarum. However, the therapeutic relevance of MIMP in IBD remains unknown. Methods: We initially employed a dextran sodium sulphate (DSS)-induced colitis model and evaluated the effect of MIMP on the inflammation response, intestinal barrier and gut microbiota using histological examination, Fluorescein isothiocyanate-Dextran detection and pyrosequencing analysis respectively. We then established peripheral blood mononuclear cells (PBMCs) and an epithelial CaCO-2 co-culture model to investigate the regulatory role of MIMP in inflammatory cytokines. The level changes of inflammatory cytokines were detected using Enzyme-linked immunosorbent and real-time polymerase chain reaction assay. The involved regulatory mechanisms were investigated mainly using dual luciferase reporter and chromatin immunoprecipitation assay. Results: In the DSS-induced colitis model, we observed that MIMP intervention effectively improved the body weight loss, increased the colon length and decreased disease activity index. Consistently, the inflammation scores in the MIMP treatment group were significantly lower than those in the DSS treatment group. Furthermore, MIMP intervention was found to successfully neutralize DSS treatment by decreasing the expression of pro-inflammatory cytokines (IFN-γ, IL-17 and IL-23) and increasing the expression of anti-inflammatory cytokines (IL-4 and IL-10). Notably, the permeability assay demonstrated that the MIMP treatment group was remarkably lower than that in the DSS treatment group. We also showed that MIMP improved gut microbiota dysbiosis caused by DSS-induced inflammation. Additionally, in PBMCs and the CaCO-2 co-culture model, MIMP showed an obvious suppressive effect on lipopolysaccharide-induced inflammation in a time- and dose-dependent manner. Furthermore, we revealed that MIMP could modulate inflammatory cytokine expression through the toll-like receptor 4 pathway and histone acetylation. Conclusions: Our results suggested that MIMP showed a significant anti-inflammatory effect through regulating the gut barrier, microbiota and inflammatory cytokines. MIMP may have translational relevance as clinically relevant therapy for IBD patients.

Oral Probiotics Ameliorate the Behavioral Deficits Induced by Chronic Mild Stress in Mice via the Gut Microbiota-Inflammation Axis

“…Many bacteria in the genus Lactobacillus can be used as probiotics and are distinguished for their immunomodulatory actions and therapeutic applications. Micro integral membrane protein, a newly discovered anti-inflammatory protein of L. plantarum , protects gut barrier function and modulates microbiota and inflammatory cytokines ( Yin et al, 2018 ). Lactobacillus are able to control a wide range of bacterial strains by secreting antimicrobial factors ( Mazaya et al, 2015 ).…”

Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier

“…Micro integral membrane proteins (MIMPs) were identified as the smallest domain from the SLPs of L. plantarum [31]. Previous studies have shown that MIMPs of L. plantarum CGMCC 1258 can restore tight junctional injury by increasing the expression of tight junction proteins including JAM-1, occludin, and claudin-1, which can allow the transportation of ions and small molecules of soluble substances through gut barrier, but prevent the passage of toxic large molecules and microorganisms [32].…”

The Effectiveness of Probiotics in the Treatment of Inflammatory Bowel Disease (IBD)—A Critical Review

“…Nevertheless, the direct pathway of this protection needs further investigation. In other studies, Yin and co-workers [ 126 ] isolated the Micro Integral Membrane Protein (MIMP) from Lactobacillus plantarum . These particles affected the Caco-2 cell line, reducing its permeability.…”