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Cell Physiol Biochem. 2018;45(2):474-490. doi: 10.1159/000487027. Epub 2018 Jan 25.

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

Yin M1,2, Yan X1, Weng W3,4, Yang Y1,5, Gao R1, Liu M6, Pan C1, Zhu Q1, Li H1, Wei Q7, Shen T1, Ma Y1,8,5, Qin H1.

Author information

1
Department of GI Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
2
Department of General Surgery, Anhui NO.2 Province People's Hopital, Hefei, China.
3
Department of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.
4
Center for Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China.
5
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
6
Department of Hepatobiliary Surgery, Affiliated Wuxi No.3 Hospital, Nantong University, Wuxi, China.
7
Department of Pathology, Shanghai Tenth People's Hospital Affiliated to Tongji University, Shanghai, China.
8
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

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.

KEYWORDS:

Gut barrier; Inflammatory bowel disease; Inflammatory cytokines; MIMP; Microbiota

PMID:
29402771
DOI:
10.1159/000487027
[Indexed for MEDLINE]
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