Versatility of bacterial outer membrane vesicles in regulating intestinal homeostasis

Outer membrane vesicles (OMVs) play vital roles in bacterial communication both intraspecifically and interspecifically. However, extracellular mechanisms of gut microbiota-derived OMVs in the intestine remain poorly understood. Here, we report that OMVs released from Akkermansia muciniphila are able to (i) restore disturbed balance of the gut microbiota by selectively promoting the proliferation of beneficial bacteria through membrane fusion, (ii) elicit mucosal immunoglobulin A response by translocating into Peyer's patches and subsequently activating B cells and dendritic cells, and (iii) maintain the integrity of the intestinal barrier by entering intestinal epithelial cells to stimulate the expressions of tight junctions and mucus. We demonstrate that transplantation of gut microbiota-associated OMVs to the intestine can alleviate colitis and enhance anti-programmed cell death protein 1 therapy against colorectal cancer by regulating intestinal homeostasis. This work discloses the importance of gut microbiota-derived OMVs in intestinal ecology, providing an alternative target for disease intervention and treatment.

Automated summary

Outer membrane vesicles (OMVs) released by Akkermansia muciniphila can restore gut microbiota balance, stimulate mucosal immunoglobulin A response, and maintain intestinal barrier integrity by entering intestinal epithelial cells. Transplanting gut microbiota-derived OMVs can alleviate colitis and enhance anti-PD-1 therapy against colorectal cancer. This study highlights the important role of gut microbiota-derived OMVs in intestinal ecology and provides a new target for disease intervention and treatment.