Abstract
Emerging evidence suggests that altered gut microbiota is linked to community-acquired pneumonia (CAP), but the potential mechanisms by which gut microbiota and its metabolites contribute to the development of CAP remain unclear. Fecal samples from 32 CAP patients and 36 healthy controls were analyzed through metagenomic sequencing and metabolomic profiling. The gut microbiota composition in CAP patients showed significant differences and lower diversity compared to healthy controls. Genera involved in short-chain fatty acid (SCFA) production, such as Faecalibacterium, Ruminococcus, and Eubacterium, as well as species like Faecalibacterium prausnitzii, Bifidobacterium adolescentis, Eubacterium rectale, Prevotella copri, and Ruminococcus bromii, were significantly depleted in CAP patients. Bacterial co-occurrence network analysis revealed an over-representation of pro-inflammatory bacteria, which contributed to the core gut microbiome in CAP patients. Metabolomic analysis of fecal samples identified a distinct metabolic profile, with a notable increase in arachidonic acid, but a decrease in secondary bile acids, such as deoxycholic acid, lithocholic acid, and ursodeoxycholic acid, compared to healthy controls. Spearman correlation analysis between differential microbiota and bile acids showed that Faecalibacterium prausnitzii, Bifidobacterium adolescentis, Eubacterium rectale, and Prevotella copri were positively correlated with ursocholic acid, lithocholic acid, and ursodeoxycholic acid, respectively. Our results suggest that the reduction in secondary bile acids, insufficient production of SCFAs, and an overabundance of pro-inflammatory bacteria may contribute to metabolic inflammation in the body. These factors could play a key role in the pathogenesis of CAP, driven by gut microbiota alterations. IMPORTANCE: This study presents a comprehensive metagenomic and metabolomic analysis of fecal samples from community-acquired pneumonia (CAP) patients, identifying key characteristics, such as decreased secondary bile acids, imbalanced short-chain fatty acid production, and increased pro-inflammatory bacteria. These findings provide valuable insights into the mechanisms linking gut microbiota alterations to CAP pathogenesis and suggest that targeting the gut microbiota could be a promising strategy for intervening in CAP.