Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions

Abstract

The gut microbiota has an important role in the gut barrier, inflammation and metabolic functions. Studies have identified a close association between the intestinal barrier and metabolic diseases, including obesity and type 2 diabetes (T2D). Recently, Akkermansia muciniphila has been reported as a beneficial bacterium that reduces gut barrier disruption and insulin resistance. Here we evaluated the role of A. muciniphila-derived extracellular vesicles (AmEVs) in the regulation of gut permeability. We found that there are more AmEVs in the fecal samples of healthy controls compared with those of patients with T2D. In addition, AmEV administration enhanced tight junction function, reduced body weight gain and improved glucose tolerance in high-fat diet (HFD)-induced diabetic mice. To test the direct effect of AmEVs on human epithelial cells, cultured Caco-2 cells were treated with these vesicles. AmEVs decreased the gut permeability of lipopolysaccharide-treated Caco-2 cells, whereas Escherichia coli-derived EVs had no significant effect. Interestingly, the expression of occludin was increased by AmEV treatment. Overall, these results imply that AmEVs may act as a functional moiety for controlling gut permeability and that the regulation of intestinal barrier integrity can improve metabolic functions in HFD-fed mice. Secretions from a particular gut bacterium improve metabolic function and glucose tolerance in mice with type II diabetes. Gut bacteria are crucial to maintaining the intestinal barrier, which separates gut contents from the rest of the body and protects from external pathogens. Following a study demonstrating that levels of the gut bacterium Akkermansia muciniphila are reduced in obese people, Sung Ho Ryu at Pohang University of Science and Technology and Yoon-Keun Kim at MD Healthcare Inc, South Korea, and co-workers, investigated the role of A.muciniphila in type II diabetes. They found that lipid structures termed extracellular vesicles (EVs) secreted by A.muciniphila were more prolific in the faeces of healthy patients than those with type II diabetes. Administration of these bacterial EVs to diabetic mice enhanced gut barrier wall integrity, reduced weight gain and improved glucose tolerance.