Exp Mol Med.  2018 Feb;50(2):e450. 10.1038/emm.2017.282.

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

• Chelakkot
• Choi Y
• Kim DK
• Park HT
• Ghim J
• Kwon Y
• Jeon J
• Kim MS
• Jee YK
• Gho YS
• Park HS
• Kim YK
• Ryu SH

• KMID: 2440032
• DOI: http://doi.org/10.1038/emm.2017.282

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.

MeSH Terms

Animals
Body Weight
Caco-2 Cells
Diet, High-Fat
Epithelial Cells
Escherichia
Extracellular Vesicles*
Gastrointestinal Microbiome
Glucose
Humans
Inflammation
Insulin Resistance
Metabolic Diseases
Mice
Obesity
Occludin
Permeability*
Tight Junctions*
Glucose
Occludin