Effect of Extracelluar Vesicles Derived from Akkermansia muciniphila on Intestinal Barrier in Colitis Mice

Abstract

Inflammatory bowel disease (IBD) is a chronic and recurrent disease. It has been observed that the incidence and prevalence of IBD are increasing, which consequently raises the risk of developing colon cancer. Recently, the regulation of the intestinal barrier by probiotics has become an effective treatment for colitis. Akkermansia muciniphila-derived extracellular vesicles (Akk EVs) are nano-vesicles that contain multiple bioactive macromolecules with the potential to modulate the intestinal barrier. In this study, we used ultrafiltration in conjunction with high-speed centrifugation to extract Akk EVs. A lipopolysaccharide (LPS)-induced RAW264.7 cell model was established to assess the anti-inflammatory effects of Akk EVs. It was found that Akk EVs were able to be absorbed by RAW264.7 cells and significantly reduce the expression of nitric oxide (NO), TNF-α, and IL-1β (p < 0.05). We explored the preventative effects on colitis and the regulating effects on the intestinal barrier using a mouse colitis model caused by dextran sulfate sodium (DSS). The findings demonstrated that Akk EVs effectively prevented colitis symptoms and reduced colonic tissue injury. Additionally, Akk EVs significantly enhanced the effectiveness of the intestinal barrier by elevating the expression of MUC2 (0.53 ± 0.07), improving mucus integrity, and reducing intestinal permeability (p < 0.05). Moreover, Akk EVs increased the proportion of the beneficial bacteria Firmicutes (33.01 ± 0.09%) and downregulated the proportion of the harmful bacteria Proteobacteria (0.32 ± 0.27%). These findings suggest that Akk EVs possess the ability to regulate immune responses, protect intestinal barriers, and modulate the gut microbiota. The research presents a potential intervention approach for Akk EVs to prevent colitis.

A multi-omics approach to investigate characteristics of gut microbiota and metabolites in hypertension and diabetic nephropathy SPF rat models

“…We also found enriched abundance of Akkermansia muciniphila (phylum Verrucomicrobia ) in the HDN group, Akkermansia aids in the development and preservation of the intestinal mucus layer, improves the functionality of the intestinal barrier, inhibits the proliferation of detrimental bacteria, and diminishes the concentration of intestinal endotoxins, thus protecting intestinal health (Zheng et al, 2023 ). Akkermansia reduces the risk of obesity, diabetes, enteritis, colon cancer and other diseases (Li et al, 2023 ; Zheng et al, 2023 ). However, the abundance of A. muciniphila is increased in experimental animals and humans with CKD (Lakshmanan et al, 2021 ), accompanied by an increase in indoxyl sulfate and p-cresyl sulfate (pCS).…”

Targeting the Gut: A Systematic Review of Specific Drug Nanocarriers

“…EVs derived from the intestinal microbiome can represent ideal mucophilic drug carriers, as they are intrinsically able to pass through the aseptic mucous layer of the colon by different routes, enter the border intestinal epithelial cells, interact with mucosal immune cells and the intestinal vascular system, and promote its wide and systemic spread. Zheng et al demonstrated in a mouse model of colitis that EVs derived from the bacterium Akkermansia muciniphila , a mucophilic member of the gut microbiota, prevent disease symptoms by reducing mucosal damage and increase the expression of MUC2 [ 151 ]. The reparation of mucosal damage on colon tissue was also demonstrated using EVs derived from B. acidifaciens in a colitis mouse model, with a complete restoration of the mucus and gut microbiota balance [ 152 ].…”

Unveiling the Potential of Extracellular Vesicles as Biomarkers and Therapeutic Nanotools for Gastrointestinal Diseases

“…They offer diverse therapeutic alternatives such as anti-infection, anti-inflammation, anti-tumor, anti-aging, and more [ 24 ]. Furthermore, Zheng et al demonstrated the therapeutic potential of BEVs derived from Akkermansia muciniphila in reducing mucosal damage, increasing MUC2 expression, and subsequently improving mucus integrity, leading to a reduction in the intestinal permeability in mice with colitis [ 25 ]. Similarly, BEVs derived from Bifidobacterium acidifaciens were shown to induce the repair of mucosal damage and achieve complete restoration of the mucus and gut microbiota balance in mice with dextran sulfate sodium (DSS)-induced colitis [ 26 ].…”