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Extracellular vesicle miRNAs promote the intestinal microenvironment by interacting with microbes in colitis
Qichen Shen1, Zhuizui Huang1, Lingyan Ma2
1Department of Biotechnology, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, China.
Abstract:
Inflammatory bowel disease (IBD) is a global disease with no cure. Disruption of the microbial ecosystem is considered to be an important cause of IBD. Extracellular vesicles (EVs) are vital participants in cell-cell and cell-organism communication. Both host-derived EVs and bacteria-derived membrane vesicles (OMVs) contribute to homeostasis in the intestine. However, the roles of EVs-miRNAs and MVs in host-microbe interactions in colitis remain unclear. In the present study, the animal model of colitis was established by dextran sulfate sodium (DSS) to investigate the changes of miRNAs in colonic EVs from colitis. Several miRNAs were significantly altered in colitis EVs. miR-181b-5p transplantation inhibited M1 macrophage polarization and promoted M2 polarization to reduce the levels of inflammation both in acute and remission of chronic colitis. miR-200b-3p could interact with bacteria and regulate the composition of the microbiota, which contributed to intestinal barrier integrity and homeostasis. Notably, MVs from normal feces could effectively reverse the composition of the intestinal microbiota, restore the intestinal barrier and rescue colitis, and BMVs from colitis would also have similar effects after miR-200b-3p treatment. Our results preliminarily identify a vesicle-based host-microbe interaction cycle in colitis and provide new ideas for colitis treatment.
Insights
Extracellular vesicles (EVs) and bacterial membrane vesicles (MVs) play key roles in inflammatory bowel disease (IBD). Specific microRNAs (miRNAs) within these vesicles, like miR-181b-5p and miR-200b-3p, show therapeutic potential for colitis by modulating host-microbe interactions.
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- Inflammatory bowel disease (IBD) is a global health concern linked to gut microbial dysbiosis.
- Extracellular vesicles (EVs) and outer membrane vesicles (OMVs) mediate host-microbe communication in the intestine.
- The specific roles of EV-miRNAs and MVs in the pathogenesis and progression of colitis are not fully understood.
Purpose of the Study:
- To investigate the alterations in colonic EVs-miRNAs in a dextran sulfate sodium (DSS)-induced colitis mouse model.
- To explore the therapeutic potential of specific miRNAs and MVs in modulating host-microbe interactions and alleviating colitis.
Main Methods:
- Induction of colitis in a mouse model using DSS.
- Isolation and analysis of miRNAs from colonic EVs.
- Investigating the effects of miR-181b-5p and miR-200b-3p on macrophage polarization and microbiota composition.
- Assessing the therapeutic efficacy of fecal MVs and engineered BMVs in colitis models.
Main Results:
- Significant alterations in miRNA profiles within colonic EVs were observed in colitis.
- miR-181b-5p transplantation reduced inflammation by shifting macrophage polarization from M1 to M2.
- miR-200b-3p interacted with bacteria, enhanced intestinal barrier integrity, and restored homeostasis.
- Normal fecal MVs and colitis-derived BMVs (treated with miR-200b-3p) reversed microbiota dysbiosis and ameliorated colitis.
Conclusions:
- A vesicle-mediated host-microbe interaction cycle in colitis is identified.
- EVs-miRNAs and MVs represent promising therapeutic targets for IBD treatment.
- This study offers novel strategies for managing colitis through modulation of the gut microbiome and host-vesicle communication.
