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

Akkermansia muciniphila-derived extracellular vesicles influence gut permeability through the regulation of tight junctions.
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DOI:
10.1038/emm.2017.282
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发表时间:
2018-02-23
影响因子:
12.8
通讯作者:
Ryu SH
Ryu SH
中科院分区:
医学2区
文献类型:
--
作者:
Chelakkot C;Choi Y;Kim DK;Park HT;Ghim J;Kwon Y;Jeon J;Kim MS;Jee YK;Gho YS;Park HS;Kim YK;Ryu SH

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肠道菌群在肠道屏障,炎症和代谢功能中具有重要作用。研究已经确定了肠道屏障和代谢疾病(包括肥胖症和2型糖尿病(T2D))之间的密切关联。最近,据报道,阿克氏菌是一种有益细菌,可降低肠道屏障的破坏和胰岛素抵抗。在这里,我们评估了粘曲霉的细胞外囊泡(AMEV)在肠道通透性调节中的作用。我们发现,与T2D患者相比,健康对照的粪便样本中有更多的AMEV。此外,AMEV给药增强了紧密的连接功能,体重增加降低并提高了高脂饮食(HFD)诱导的糖尿病小鼠的葡萄糖耐受性。为了测试AMEV对人上皮细胞的直接作用,用这些囊泡处理培养的Caco-2细胞。 AMEV降低了脂多糖处理的CACO-2细胞的肠道渗透性,而大肠含量的Coli-coli-colded EVS没有显着作用。有趣的是,通过AMEV治疗增加了occludin的表达。总体而言,这些结果表明,AMEV可以充当控制肠道渗透性的功能部分,并且调节肠道屏障完整性可以改善HFD喂养小鼠的代谢功能。
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.
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