Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines
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 Plan...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Cell Physiol Biochem Press GmbH & Co KG
2018-01-01
|
| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/487027 |
| _version_ | 1811267957295153152 |
|---|---|
| author | Mingming Yin Xuebing Yan Wenhao Weng Yongzhi Yang Renyuan Gao Minfeng Liu Cheng Pan Qi Zhu Hao Li Qing Wei Tongyi Shen Yanlei Ma Huanlong Qin |
| author_facet | Mingming Yin Xuebing Yan Wenhao Weng Yongzhi Yang Renyuan Gao Minfeng Liu Cheng Pan Qi Zhu Hao Li Qing Wei Tongyi Shen Yanlei Ma Huanlong Qin |
| author_sort | Mingming Yin |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T21:13:16Z |
| format | Article |
| id | doaj.art-ec3ec64844e747c5a56e5671b600d0c8 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-12T21:13:16Z |
| publishDate | 2018-01-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-ec3ec64844e747c5a56e5671b600d0c82022-12-22T03:16:32ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-01-0145247449010.1159/000487027487027Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory CytokinesMingming YinXuebing YanWenhao WengYongzhi YangRenyuan GaoMinfeng LiuCheng PanQi ZhuHao LiQing WeiTongyi ShenYanlei MaHuanlong QinBackground/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.https://www.karger.com/Article/FullText/487027Inflammatory bowel diseaseMIMPGut barrierMicrobiotaInflammatory cytokines |
| spellingShingle | Mingming Yin Xuebing Yan Wenhao Weng Yongzhi Yang Renyuan Gao Minfeng Liu Cheng Pan Qi Zhu Hao Li Qing Wei Tongyi Shen Yanlei Ma Huanlong Qin Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines Cellular Physiology and Biochemistry Inflammatory bowel disease MIMP Gut barrier Microbiota Inflammatory cytokines |
| title | Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines |
| title_full | Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines |
| title_fullStr | Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines |
| title_full_unstemmed | Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines |
| title_short | Micro Integral Membrane Protein (MIMP), a Newly Discovered Anti-Inflammatory Protein of Lactobacillus Plantarum, Enhances the Gut Barrier and Modulates Microbiota and Inflammatory Cytokines |
| title_sort | micro integral membrane protein mimp a newly discovered anti inflammatory protein of lactobacillus plantarum enhances the gut barrier and modulates microbiota and inflammatory cytokines |
| topic | Inflammatory bowel disease MIMP Gut barrier Microbiota Inflammatory cytokines |
| url | https://www.karger.com/Article/FullText/487027 |
| work_keys_str_mv | AT mingmingyin microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT xuebingyan microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT wenhaoweng microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT yongzhiyang microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT renyuangao microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT minfengliu microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT chengpan microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT qizhu microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT haoli microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT qingwei microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT tongyishen microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT yanleima microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines AT huanlongqin microintegralmembraneproteinmimpanewlydiscoveredantiinflammatoryproteinoflactobacillusplantarumenhancesthegutbarrierandmodulatesmicrobiotaandinflammatorycytokines |