Butyrate protects against MRSA pneumonia via regulating gut-lung microbiota and alveolar macrophage M2 polarization

作者：Yan Zhao, Haoming Sun, Yiwei Chen, Qiang Niu, Yiting Dong, Mei Li, Ye Yuan, Xiaojun Yang, Qingzhu Sun · 发表于：mBio · 年份：2023 · DOI：10.1128/mbio.01987-23 · 被引用次数：52 · 研究领域：Gut microbiota and health、Pediatric health and respiratory diseases、Epigenetics and DNA Methylation

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) is a well-recognized cause of bacterial pneumonia in general. The gut microbiota and their metabolic byproducts act as important modulators of the gut-lung axis. Our investigation indicates a significant reduction in the abundance of butyrate producer unclassified_f__ Lachnospiraceae within the lung and gut microbiota of MRSA-infected mice, as well as a significant decrease in the levels of butyrate in gut and serum. Additionally, supplementary sodium butyrate (NaB) significantly reduces bacteria colonization in the lung, suppresses pro-inflammatory cytokines expression, and enhances lung tissue morphology in MRSA-treated mice. The results of high-throughput 16S rDNA sequencing demonstrate that NaB reshapes the gut and lung microbiota by drastically reducing the abundance of potential pathogenic bacteria in the gut and cell motility-related bacteria in the lung, which are induced by MRSA. Moreover, NaB treatment augments the gut and circulating butyrate levels. Mechanistically, NaB promotes signal transducer and activator of transcription 1 (STAT1) acetylation and inhibits dimer STAT1 phosphorylation by reducing the binding of histone deacetylase 3 to STAT1, thereby altering alveolar macrophage polarization toward the M2 phenotype. Collectively, our findings suggest that NaB exerts a preventative effect against MRSA-induced pneumonia by enhancing the gut-lung microbiota and promoting macrophage polarization toward an...