Odoribacter splanchnicus-derived extracellular vesicles alleviate inflammatory bowel disease by modulating gastrointestinal inflammation and intestinal barrier function via the NLRP3 inflammasome suppression.
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Abstract
Background: Extracellular vesicles (EVs) derived from specific bacteria exert therapeutic potential on inflammatory diseases. Previous reports suggest the protective role of Odoribacter splanchnicus (O.splanchnicus) in inflammatory bowel disease (IBD). The effect of EVs derived from O.splanchnicus (Os-EVs) and the underlying mechanism on IBD were surveyed here.
Methods: Os-EVs were derived with ultracentrifugation before characterization by transmission electron microscopy and nanoparticle tracking analysis. Based on IBD model mice induced by dextran sulfate sodium (DSS), the effects of Os-EVs on IBD symptoms, intestinal barrier dysfunction, and colonic apoptosis, inflammation as well as NLRP3 inflammasome activation were analyzed. NLRP3 knockout mice were exploited to judge the role of NLRP3 in Os-EVs against IBD.
Results: Os-EVs were typically shaped as a double concave disc (average diameter = 95 nm). The administration of Os-EVs attenuated DSS-induced body weight loss, colon shortening, disease activity index score, and histological injury in mice. Os-EVs could also relieve intestinal barrier dysfunction and colonic apoptosis, as evidenced by the up-regulation of zona occludens-1 and Occludin and the decrease of TUNEL-positive staining in colonic tissues of IBD mice. Os-EVs downregulated the expression of the interleukin-1β (IL-1β), tumor necrosis factor-α, and IL-6, and elevated IL-10, accompanied by blockage of the NLRP3 inflammasome activation in DSS-induced mice. Furthermore, NLRP3 knockout mice experiments revealed that the protective role of Os-EVs in IBD relies on regulating NLRP3.
Conclusion: Our finding indicated that Os-EVs effectively ameliorated IBD through repressing NLRP3, strongly supporting the potential of probiotic-derived EVs for alleviating IBD.
期刊介绍：
Molecular Medicine is an open access journal that focuses on publishing recent findings related to disease pathogenesis at the molecular or physiological level. These insights can potentially contribute to the development of specific tools for disease diagnosis, treatment, or prevention. The journal considers manuscripts that present material pertinent to the genetic, molecular, or cellular underpinnings of critical physiological or disease processes. Submissions to Molecular Medicine are expected to elucidate the broader implications of the research findings for human disease and medicine in a manner that is accessible to a wide audience.
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