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<p>Neuroinflammation and impaired barrier function are two prominent pathological mechanisms contributing to cognitive impairment in patients with vascular dementia (VaD). Currently, effective treatments for VaD remain limited, underscoring the clinical significance of developing novel, multi-targeted therapeutic strategies. In recent years, more and more studies have shown the connection between lung and brain, so we used nasal administration of probiotics to observe the improvement of cognitive function in VaD rats. Because the safety of the organism is uncertain, the study develop a bacterial extracellular vesicles (EVs) drug delivery system that delivers the key bioactive metabolite asperuloside (ASP) by modulating the microbiota–lung–brain axis, aiming to improve brain targeting and therapeutic outcomes. The results show that nasal administration of <i>L. salivarius</i> significantly ameliorated cognitive impairment, mitigated neuroinflammation, restored blood-brain barrier and lung barrier function, and modulated lung flora in VaD rats. Metabolomics analysis identified ASP as the principal active metabolite, although its efficacy as a standalone agent was constrained. The EA system effectively facilitated ASP delivery to brain tissue, yielding neuroprotective and barrier-repair effects. Collectively, our study shows that <i>L. salivarius</i> can modulate the pathophysiological processes of VaD via the “microbiota-lung-brain axis.” Its EVs serve as effective vehicles for delivering active metabolites, offering a novel integrated therapeutic approach for VaD involving microbial metabolism delivery.</p>

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The lung-brain axis mediates the neuroprotective effects of nasally administered L. salivarius and its EV-delivered metabolite in vascular dementia

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月12日

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  • Cihua Zheng,
  • Zhuoya Wang,
  • Furui Tang,
  • Yuchun Zhong,
  • Jiacheng Zheng,
  • Jian Xie,
  • Li Liu,
  • Yimin Pi,
  • Xifeng Wang,
  • Tian Liu,
  • Zhidong He,
  • Jun Luo

摘要

Neuroinflammation and impaired barrier function are two prominent pathological mechanisms contributing to cognitive impairment in patients with vascular dementia (VaD). Currently, effective treatments for VaD remain limited, underscoring the clinical significance of developing novel, multi-targeted therapeutic strategies. In recent years, more and more studies have shown the connection between lung and brain, so we used nasal administration of probiotics to observe the improvement of cognitive function in VaD rats. Because the safety of the organism is uncertain, the study develop a bacterial extracellular vesicles (EVs) drug delivery system that delivers the key bioactive metabolite asperuloside (ASP) by modulating the microbiota–lung–brain axis, aiming to improve brain targeting and therapeutic outcomes. The results show that nasal administration of L. salivarius significantly ameliorated cognitive impairment, mitigated neuroinflammation, restored blood-brain barrier and lung barrier function, and modulated lung flora in VaD rats. Metabolomics analysis identified ASP as the principal active metabolite, although its efficacy as a standalone agent was constrained. The EA system effectively facilitated ASP delivery to brain tissue, yielding neuroprotective and barrier-repair effects. Collectively, our study shows that L. salivarius can modulate the pathophysiological processes of VaD via the “microbiota-lung-brain axis.” Its EVs serve as effective vehicles for delivering active metabolites, offering a novel integrated therapeutic approach for VaD involving microbial metabolism delivery.