Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling

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 immu...

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Main Authors: Hongxia Zhou, Wenbo Huang, Jieting Li, Peier Chen, Lihan Shen, Wenjing Huang, Kailin Mai, Heyan Zou, Xueqin Shi, Yunceng Weng, Yuhua Liu, Zifeng Yang, Caiwen Ou
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Language:English
Published: KeAi Communications Co., Ltd. 2025-03-01
Series:Bioactive Materials
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Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X24005000
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author Hongxia Zhou
Wenbo Huang
Jieting Li
Peier Chen
Lihan Shen
Wenjing Huang
Kailin Mai
Heyan Zou
Xueqin Shi
Yunceng Weng
Yuhua Liu
Zifeng Yang
Caiwen Ou
author_facet Hongxia Zhou
Wenbo Huang
Jieting Li
Peier Chen
Lihan Shen
Wenjing Huang
Kailin Mai
Heyan Zou
Xueqin Shi
Yunceng Weng
Yuhua Liu
Zifeng Yang
Caiwen Ou
author_sort Hongxia Zhou
collection DOAJ
description 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 Lactobacillus reuteri 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 IL-17a. 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.
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spelling doaj-art-1ee2602864cc405180224d02a8839c012025-01-26T05:04:22ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2025-03-0145401416Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signalingHongxia Zhou0Wenbo Huang1Jieting Li2Peier Chen3Lihan Shen4Wenjing Huang5Kailin Mai6Heyan Zou7Xueqin Shi8Yunceng Weng9Yuhua Liu10Zifeng Yang11Caiwen Ou12Dongguan Institute of Respiratory and Critical Care Medicine, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523018, ChinaState 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, ChinaState 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, ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523018, ChinaDongguan Institute of Respiratory and Critical Care Medicine, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523018, ChinaState 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, ChinaState 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, ChinaDongguan Institute of Respiratory and Critical Care Medicine, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523018, ChinaThe Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523018, ChinaBecton Dickinson Medical Devices (Shanghai) Co., Ltd., Guangzhou, 510180, ChinaDepartment of General Practice, The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523018, China; Corresponding author. The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's. Hospital), Southern Medical University, 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; Guangzhou National Laboratory, Guangzhou, 510000, China; State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau SAR, 519020, China; Corresponding author. 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.The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523018, China; Corresponding author. The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's. Hospital), Southern Medical University, Dongguan, 523018, China.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 Lactobacillus reuteri 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 IL-17a. 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.http://www.sciencedirect.com/science/article/pii/S2452199X24005000Extracellular vesiclesIAVLactobacillus reuteriInflammationIL-17
spellingShingle Hongxia Zhou
Wenbo Huang
Jieting Li
Peier Chen
Lihan Shen
Wenjing Huang
Kailin Mai
Heyan Zou
Xueqin Shi
Yunceng Weng
Yuhua Liu
Zifeng Yang
Caiwen Ou
Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling
Bioactive Materials
Extracellular vesicles
IAV
Lactobacillus reuteri
Inflammation
IL-17
title Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling
title_full Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling
title_fullStr Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling
title_full_unstemmed Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling
title_short Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling
title_sort oral probiotic extracellular vesicle therapy mitigates influenza a virus infection via blunting il 17 signaling
topic Extracellular vesicles
IAV
Lactobacillus reuteri
Inflammation
IL-17
url http://www.sciencedirect.com/science/article/pii/S2452199X24005000
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