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Background <p>Acute respiratory distress syndrome (ARDS) is a severe clinical syndrome with limited therapeutic options. Acute lung injury (ALI) is widely used as an experimental animal model that recapitulates the key pathological features of human ARDS. <i>Parabacteroides goldsteinii</i>, a newly identified Gram-negative probiotic, exhibits anti-inflammatory effects in certain disease models. Gram-negative bacteria release nanoscale structures called outer membrane vesicles (OMVs), which show varying composition across species. The role of <i>P. goldsteinii</i>-derived OMVs (Pg-OMVs) in ALI or ARDS remains to be elucidated.</p> Result <p>In this study, we investigated the therapeutic potential of Pg-OMVs in a bleomycin (BLM)-induced ALI mouse model and explored their effects on pulmonary inflammation and gut microbiota composition. Compared to mice receiving BLM alone, Pg-OMV-treated mice exhibited significantly reduced inflammatory cell infiltration and lower levels of pro-inflammatory cytokines. Notably, Pg-OMV treatment significantly altered the gut microbiota composition, characterized by an increased abundance of <i>Akkermansia muciniphila</i> and a decreased abundance of <i>Clostridia_bacterium</i>. Fecal microbiota transplantation (FMT) experiments confirmed that the protective effects of Pg-OMVs were mediated via gut-lung axis. Further analysis revealed elevated cholic acid (CA) levels in the peripheral blood and bronchoalveolar lavage fluid following Pg-OMV treatment. CA was shown to suppress BLM-induced macrophage pyroptosis in the lung. Pharmacological inhibition of CA reversed the protective effects of Pg-OMVs, further confirming its pivotal role.</p> Conclusions <p>In summary, Pg-OMVs increased the abundance of <i>Akkermansia muciniphila</i> while decreasing the abundance of <i>Clostridia_bacterium</i> in the gut, elevated systemic CA levels, and suppressed macrophage pyroptosis via inhibition of the NF-κB pathway, thereby attenuating pulmonary inflammation and ultimately alleviating ALI. These findings highlight a novel therapeutic strategy for the treatment of ALI or ARDS by targeting the gut-lung axis.</p> Graphical abstract <p></p>

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Parabacteroides goldsteinii-derived outer membrane vesicles alleviate acute lung injury via modulation of bile acid metabolism

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月18日

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  • Wensi Zhu,
  • Linxiao Han,
  • Ludan He,
  • Shuoyan Wei,
  • Juan Li,
  • Liangcao Xin,
  • Haiyun Zhang,
  • Jie Shen,
  • Yuanlin Song,
  • Jiebai Zhou,
  • Chih-Jung Chang,
  • Jian Zhou

摘要

Background

Acute respiratory distress syndrome (ARDS) is a severe clinical syndrome with limited therapeutic options. Acute lung injury (ALI) is widely used as an experimental animal model that recapitulates the key pathological features of human ARDS. Parabacteroides goldsteinii, a newly identified Gram-negative probiotic, exhibits anti-inflammatory effects in certain disease models. Gram-negative bacteria release nanoscale structures called outer membrane vesicles (OMVs), which show varying composition across species. The role of P. goldsteinii-derived OMVs (Pg-OMVs) in ALI or ARDS remains to be elucidated.

Result

In this study, we investigated the therapeutic potential of Pg-OMVs in a bleomycin (BLM)-induced ALI mouse model and explored their effects on pulmonary inflammation and gut microbiota composition. Compared to mice receiving BLM alone, Pg-OMV-treated mice exhibited significantly reduced inflammatory cell infiltration and lower levels of pro-inflammatory cytokines. Notably, Pg-OMV treatment significantly altered the gut microbiota composition, characterized by an increased abundance of Akkermansia muciniphila and a decreased abundance of Clostridia_bacterium. Fecal microbiota transplantation (FMT) experiments confirmed that the protective effects of Pg-OMVs were mediated via gut-lung axis. Further analysis revealed elevated cholic acid (CA) levels in the peripheral blood and bronchoalveolar lavage fluid following Pg-OMV treatment. CA was shown to suppress BLM-induced macrophage pyroptosis in the lung. Pharmacological inhibition of CA reversed the protective effects of Pg-OMVs, further confirming its pivotal role.

Conclusions

In summary, Pg-OMVs increased the abundance of Akkermansia muciniphila while decreasing the abundance of Clostridia_bacterium in the gut, elevated systemic CA levels, and suppressed macrophage pyroptosis via inhibition of the NF-κB pathway, thereby attenuating pulmonary inflammation and ultimately alleviating ALI. These findings highlight a novel therapeutic strategy for the treatment of ALI or ARDS by targeting the gut-lung axis.

Graphical abstract