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<p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a major pathogen responsible for acute lung injury (ALI) and other respiratory diseases. Probiotics and their metabolic byproducts are essential regulators of the gut-lung axis. This study investigated the protective effects of a mixed probiotics combination (<i>Ligilactobacillus salivarius</i> H3, <i>Bacillus stratosphericus</i> J1366, and <i>Priestia megaterium</i> J1037), which demonstrated inhibitory activity against MRSA growth and biofilm formation in vitro, on MRSA-induced ALI in mice. Results indicated that MRSA infection exacerbated lung pathological damage (<i>P</i> &lt; 0.001), oxidative stress, and inflammation, while also disrupting gut microbiota balance and impairing intestinal barrier integrity. In contrast, the mixed probiotics restored gut microbiota homeostasis, enhanced barrier function, and increased short-chain fatty acid (SCFA) levels in the gut and circulatory system, particularly butyrate (<i>P</i> &lt; 0.05). These changes promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype (<i>P</i> &lt; 0.05), thereby reducing pulmonary bacterial load (<i>P</i> &lt; 0.05) and alleviating inflammation. 16S rDNA sequencing revealed that mixed probiotics diminished the prevalence of <i>Staphylococcus</i> (<i>P</i> &lt; 0.001) in the gut, while fostering the proliferation of beneficial genera such as <i>Lactobacillus</i> (<i>P</i> &lt; 0.001) and <i>Bifidobacterium</i> (<i>P</i> &lt; 0.05). Notably, while vancomycin treatment reduced lung bacterial load (<i>P</i> &lt; 0.05) and inflammation, it aggravated gut microbiota imbalance and barrier damage. These findings indicate that administering mixed probiotics prevents MRSA-induced ALI by regulating the gut-lung axis, providing a potential alternative to antibiotics in managing bacterial pneumonia.</p>

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Butyrate-Producing Mixed Probiotics Alleviate MRSA-Induced Acute Lung Injury in Mice by Promoting M2 Macrophage Polarization

  • 期刊论文

  • 发表日期：

    2025年4月24日

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  • Minghan Li,
  • Tianxu Pan,
  • Juntong Yu,
  • Xueting Wang,
  • Ruyi Gao,
  • Ya Wang,
  • Dongyu Zhao,
  • Xinyi Zhou,
  • Hongye Li,
  • Jialin Guo,
  • Nan Wang,
  • Haibin Huang,
  • Chunfeng Wang,
  • Guilian Yang

摘要

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for acute lung injury (ALI) and other respiratory diseases. Probiotics and their metabolic byproducts are essential regulators of the gut-lung axis. This study investigated the protective effects of a mixed probiotics combination (Ligilactobacillus salivarius H3, Bacillus stratosphericus J1366, and Priestia megaterium J1037), which demonstrated inhibitory activity against MRSA growth and biofilm formation in vitro, on MRSA-induced ALI in mice. Results indicated that MRSA infection exacerbated lung pathological damage (P < 0.001), oxidative stress, and inflammation, while also disrupting gut microbiota balance and impairing intestinal barrier integrity. In contrast, the mixed probiotics restored gut microbiota homeostasis, enhanced barrier function, and increased short-chain fatty acid (SCFA) levels in the gut and circulatory system, particularly butyrate (P < 0.05). These changes promoted the polarization of macrophages towards the anti-inflammatory M2 phenotype (P < 0.05), thereby reducing pulmonary bacterial load (P < 0.05) and alleviating inflammation. 16S rDNA sequencing revealed that mixed probiotics diminished the prevalence of Staphylococcus (P < 0.001) in the gut, while fostering the proliferation of beneficial genera such as Lactobacillus (P < 0.001) and Bifidobacterium (P < 0.05). Notably, while vancomycin treatment reduced lung bacterial load (P < 0.05) and inflammation, it aggravated gut microbiota imbalance and barrier damage. These findings indicate that administering mixed probiotics prevents MRSA-induced ALI by regulating the gut-lung axis, providing a potential alternative to antibiotics in managing bacterial pneumonia.