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<p>Outer membrane vesicles (OMVs) derived from <i>Akkermansia muciniphila</i> (<i>A. muciniphila</i>) are known to have immunomodulatory properties; however, their role in allergic asthma remains largely unexplored. In this study, we isolated OMVs from <i>A. muciniphila</i> and conjugated them with polymyxin B (PMB) to neutralize membrane-associated lipopolysaccharide (LPS). In a murine asthma model, both PMB-conjugated <i>A. muciniphila</i> OMVs (PMB-<i>A. muciniphila</i> OMVs) and native OMVs alleviated asthma symptoms, with PMB-<i>A. muciniphila</i> OMVs exhibiting superior efficacy. The enhanced therapeutic effect of PMB-<i>A. muciniphila</i> OMVs was attributable to a more potent suppression of alternative macrophage polarization (M2). Mechanistically, PMB-<i>A. muciniphila</i> 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 <i>A. muciniphila</i> 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-<i>A. muciniphila</i> OMVs present a novel and promising microbiota-derived therapeutic strategy for asthma.</p>

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Local administration of polymyxin B-conjugated Akkermansia muciniphila outer membrane vesicles attenuate asthma by suppressing M2 macrophage polarization

  • 期刊论文

  • 发表日期：

    2026年5月14日

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  • Chenchen Hou,
  • Wenhui Sun,
  • Lina Wang,
  • Xiahui Ge,
  • Qiyun Tu,
  • Huaqi Guo,
  • Tianyu Zhou,
  • Lifeng Yan,
  • Weining Xiong

摘要

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.