@article{Wang2026, 
author = {Juan Wang and Yanyan Zhang and Siqi Yuan and Mengting Zhang and Xiuwen Zhang and Jing Chen and Hanyu Dou and Hua Cheng and Xiaolei Ding},
title = {Gut probiotic Akkermansia muciniphila-derived extracellular vesicles deliver miR-21-5p to alleviate atopic dermatitis by targeting TLR4 signaling},
year = {2026},
journal = {Nano Research},
volume = {19},
number = {3},
pages = {94908421},
keywords = {inflammation, microRNA, toll-like receptor 4 (TLR4), extracellular vesicle, Akkermansia muciniphila, atopic dermatitis},
url = {https://www.sciopen.com/article/10.26599/NR.2026.94908421},
doi = {10.26599/NR.2026.94908421},
abstract = {Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, severely impairs patients’ quality of life. Mounting evidence indicates that gut microbiomes regulate AD pathogenesis through the gut-skin axis; yet the therapeutic potential of gut microbiomes-derived extracellular vesicles (EVs) remains largely unexplored. Here, we isolated EVs from gut probiotic Akkermansia muciniphila (AKK-EVs) and evaluated their therapeutic efficacy and underlying mechanisms against AD pathogenesis. AKK-EVs exhibited pronounced anti-inflammatory and antioxidant properties in vitro. MicroRNA profiling revealed that miR-21-5p was highly enriched within AKK-EVs and critically mediated their biological activity. Mechanistically, miR-21-5p directly targeted TLR4 gene, thereby suppressing NF-κB signaling pathway and downstream proinflammatory cytokine production. Notably, AKK-EVs exhibited excellent stability in gastrointestinal condition, and upon oral administration, preferentially homed to inflamed skin tissues via the gut-skin axis.Both oral and subcutaneous administration of AKK-EVs alleviated AD-like phenotypes, reshaped the inflammatory microenvironment and restored compromised skin barrier. Collectively, this study uncovers a previously unrecognized role of AKK-EVs in modulating AD and highlights probiotic-derived EVs as a promising therapeutic strategy for inflammatory skin disorders.}
}