局部施用多粘菌素B偶联的黏蛋白阿克曼菌外膜囊泡可通过抑制M2巨噬细胞极化来减轻哮喘
2026/06/01
摘要
源自粘蛋白阿克曼菌（Akkermansia muciniphila，简称A. muciniphila）的外膜囊泡（OMVs）已知具有免疫调节特性；然而，它们在过敏性哮喘中的作用在很大程度上仍未被探索。在这项研究中，我们从粘蛋白阿克曼菌中分离出OMVs，并将它们与多粘菌素B（PMB）结合，以中和与膜相关的脂多糖（LPS）。在小鼠哮喘模型中，与多粘菌素B结合的粘蛋白阿克曼菌OMVs（PMB - A. muciniphila OMVs）和天然OMVs都能缓解哮喘症状，其中PMB - A. muciniphila OMVs表现出更优的疗效。PMB - A. muciniphila OMVs增强的治疗效果归因于对替代性巨噬细胞极化（M2）更强的抑制作用。从机制上讲，PMB - A. muciniphila OMVs破坏氧化磷酸化，抑制AP - 1转录复合物和下游的PI3K/AKT信号通路，而这些对于M2极化至关重要。总之，我们的研究结果表明，通过代谢重编程和抑制AP - 1/PI3K/AKT信号通路特异性地靶向M2巨噬细胞极化，多粘菌素B结合增强了粘蛋白阿克曼菌OMVs治疗过敏性哮喘的潜力。这些发现表明，PMB - A. muciniphila OMVs为哮喘提供了一种新颖且有前景的微生物群衍生治疗策略。
Local administration of polymyxin B-conjugated Akkermansia muciniphila outer membrane vesicles attenuate asthma by suppressing M2 macrophage polarization
Chenchen Hou, Wenhui Sun, Lina Wang, Xiahui Ge, Qiyun Tu, Huaqi Guo, Tianyu Zhou, Lifeng Yan, Weining Xiong
Abstract
Outer membrane vesicles (OMVs) derived from Akkermansia muciniphila (A. muciniphila) are known to have immunomodulatory properties; however, their role in allergic asthma remains largely unexplored. In this study, we isolated OMVs from A. muciniphila and conjugated them with polymyxin B (PMB) to neutralize membrane-associated lipopolysaccharide (LPS). In a murine asthma model, both PMB-conjugated A. muciniphila OMVs (PMB-A. muciniphila OMVs) and native OMVs alleviated asthma symptoms, with PMB-A. muciniphila OMVs exhibiting superior efficacy. The enhanced therapeutic effect of PMB-A. muciniphila OMVs was attributable to a more potent suppression of alternative macrophage polarization (M2). Mechanistically, PMB-A. muciniphila OMVs disrupt oxidative phosphorylation and inhibit the AP-1 transcription complex and downstream PI3K/AKT signaling, which are essential for M2 polarization. In conclusion, our findings demonstrate that PMB conjugation augments the therapeutic potential of A. muciniphila OMVs against allergic asthma by specifically targeting M2 macrophage polarization via metabolic reprogramming and suppression of AP-1/PI3K/AKT signaling. These findings suggest that PMB-A. muciniphila OMVs present a novel and promising microbiota-derived therapeutic strategy for asthma.
源自粘蛋白阿克曼菌（Akkermansia muciniphila，简称A. muciniphila）的外膜囊泡（OMVs）已知具有免疫调节特性；然而，它们在过敏性哮喘中的作用在很大程度上仍未被探索。在这项研究中，我们从粘蛋白阿克曼菌中分离出OMVs，并将它们与多粘菌素B（PMB）结合，以中和与膜相关的脂多糖（LPS）。在小鼠哮喘模型中，与多粘菌素B结合的粘蛋白阿克曼菌OMVs（PMB - A. muciniphila OMVs）和天然OMVs都能缓解哮喘症状，其中PMB - A. muciniphila OMVs表现出更优的疗效。PMB - A. muciniphila OMVs增强的治疗效果归因于对替代性巨噬细胞极化（M2）更强的抑制作用。从机制上讲，PMB - A. muciniphila OMVs破坏氧化磷酸化，抑制AP - 1转录复合物和下游的PI3K/AKT信号通路，而这些对于M2极化至关重要。总之，我们的研究结果表明，通过代谢重编程和抑制AP - 1/PI3K/AKT信号通路特异性地靶向M2巨噬细胞极化，多粘菌素B结合增强了粘蛋白阿克曼菌OMVs治疗过敏性哮喘的潜力。这些发现表明，PMB - A. muciniphila OMVs为哮喘提供了一种新颖且有前景的微生物群衍生治疗策略。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Sci China Life Sci. 2026 May 14. doi: 10.1007/s11427-025-3240-8.）
（Sci China Life Sci. 2026 May 14. doi: 10.1007/s11427-025-3240-8.）
Local administration of polymyxin B-conjugated Akkermansia muciniphila outer membrane vesicles attenuate asthma by suppressing M2 macrophage polarization
Chenchen Hou, Wenhui Sun, Lina Wang, Xiahui Ge, Qiyun Tu, Huaqi Guo, Tianyu Zhou, Lifeng Yan, Weining Xiong
Abstract
Outer membrane vesicles (OMVs) derived from Akkermansia muciniphila (A. muciniphila) are known to have immunomodulatory properties; however, their role in allergic asthma remains largely unexplored. In this study, we isolated OMVs from A. muciniphila and conjugated them with polymyxin B (PMB) to neutralize membrane-associated lipopolysaccharide (LPS). In a murine asthma model, both PMB-conjugated A. muciniphila OMVs (PMB-A. muciniphila OMVs) and native OMVs alleviated asthma symptoms, with PMB-A. muciniphila OMVs exhibiting superior efficacy. The enhanced therapeutic effect of PMB-A. muciniphila OMVs was attributable to a more potent suppression of alternative macrophage polarization (M2). Mechanistically, PMB-A. muciniphila OMVs disrupt oxidative phosphorylation and inhibit the AP-1 transcription complex and downstream PI3K/AKT signaling, which are essential for M2 polarization. In conclusion, our findings demonstrate that PMB conjugation augments the therapeutic potential of A. muciniphila OMVs against allergic asthma by specifically targeting M2 macrophage polarization via metabolic reprogramming and suppression of AP-1/PI3K/AKT signaling. These findings suggest that PMB-A. muciniphila OMVs present a novel and promising microbiota-derived therapeutic strategy for asthma.
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小气道功能障碍可能介导体重指数与重度哮喘急性发作之间的关联
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