Zhou Hongxia, Huang Wenbo, Li Jieting, Chen Peier, Shen Lihan, Huang Wenjing, Mai Kailin, Zou Heyan, Shi Xueqin, Weng Yunceng, Liu Yuhua, Yang Zifeng, Ou Caiwen
Dongguan Institute of Respiratory and Critical Care Medicine, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523018, China.
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
Bioact Mater. 2024 Dec 3;45:401-416. doi: 10.1016/j.bioactmat.2024.11.016. eCollection 2025 Mar.
The influenza A virus (IAV) damages intestinal mucosal tissues beyond the respiratory tract. Probiotics play a crucial role in maintaining the balance and stability of the intestinal microecosystem. Extracellular vesicles (EVs) derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect. However, the specific anti-inflammatory effects and underlying mechanisms of probiotics-derived EVs on IAV remain unclear. In the present study, we investigated the therapeutic efficacy of EHA2-derived EVs (LrEVs) in a mouse model of IAV infection. Oral LrEVs were distributed in the liver, lungs, and gastrointestinal tract. In mice infected with IAV, oral LrEVs administration alleviated IAV-induced damages in the lungs and intestines, modified the microbiota compositions, and increased the levels of short-chain fatty acids in those organs. Mechanistically, LrEVs exerted their protective effects against IAV infection by blunting the pro-inflammatory IL-17 signaling. Furthermore, FISH analysis detected miR-4239, one of the most abundant miRNAs in LrEVs, in both lung and intestinal tissues. We confirmed that miR-4239 directly targets . Our findings paved the ground for future application of LrEVs in influenza treatment and offered new mechanistic insights regarding the anti-inflammatory role of miR-4239.
甲型流感病毒（IAV）会损害呼吸道以外的肠道黏膜组织。益生菌在维持肠道微生态系统的平衡与稳定方面发挥着关键作用。源自益生菌的细胞外囊泡（EVs）已成为宿主免疫反应和抗炎作用的潜在介质。然而，益生菌衍生的EVs对IAV的具体抗炎作用及其潜在机制仍不清楚。在本研究中，我们在IAV感染的小鼠模型中研究了EHA2衍生的EVs（LrEVs）的治疗效果。口服LrEVs分布于肝脏、肺和胃肠道。在感染IAV的小鼠中，口服LrEVs可减轻IAV诱导的肺和肠道损伤，改变微生物群组成，并提高这些器官中短链脂肪酸的水平。从机制上讲，LrEVs通过减弱促炎IL-17信号传导对IAV感染发挥保护作用。此外，荧光原位杂交（FISH）分析在肺和肠道组织中均检测到LrEVs中含量最丰富的miRNA之一miR-4239。我们证实miR-4239直接靶向……我们的研究结果为LrEVs在流感治疗中的未来应用奠定了基础，并为miR-4'239的抗炎作用提供了新的机制见解。
