show Abstracthide AbstractAlthough emerging evidences suggest an association between the altered gut microbiota and community-acquired pneumonia (CAP), little is known about the potential mechanisms that linked the dysbiosis of the gut microbiota and the development of CAP. In this study, we performed a metagenome-wide association study of 32 CAP patients and 36 health controls, which identified significant alterations in gut microbiota and dysbiosis-related metabolomics associated with CAP occurrence. We identified gut microbial alterations associated with CAP and linked to the changes in stool metabolites. Fecal metabolite profiles revealed that CAP patients exhibited a notable increase in Arachidonic acid, but a decrease in deoxycholic acid, lithocholic acid, ursodeoxycholic acid compared to control groups. Short-chain fatty acid-producing genera, including Faecalibacterium, Ruminococcus, and Eubacterium, and species Faecalibacterium prausnitzii, Bifidobacterium adolescentis, Eubacterium rectale, Prevotella copri, and Ruminococcus bromii, were significantly delepleted in CAP patients relative to those in control groups. Bacterial co-occurrence network analysis revealed that pro-inflammatory bacteria were over-represented and became to the core gut microbiome in CAP patients. These microbial and metabolic signatures are closely associated in CAP patients and control group. In conclusion, we identified bile acids (BAs) insufficiency, imbalanced production of short chain fatty acids (SCFAs), and excessive metabolic inflammation as gut microbiota-driven mechanisms linked to CAP. This work might explain in part the mechanistic link between altered gut microbiota and CAP pathogenesis.