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

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.