BACKGROUND: Previous studies showed airborne bacteria affect pneumonia incidence, but specific impacts of bacterial communities on Klebsiella pneumoniae infection were unknown. METHODS: Five different ratios of bacterial community structures were randomly generated. Mice were divided into control, artificial bacterial community exposure, and corresponding Klebsiella pneumoniae challenge groups. Changes in body weight, blood parameters, pulmonary pathology, inflammatory factors, metabolomics, and fecal microbiota were analyzed. RESULTS: Different bacterial community exposures had varying degrees of influence on body weight, complete blood count, inflammatory factors, alveolar lavage fluid and plasma metabolome, as well as intestinal microbiota at baseline and after infection. Metabolomic analysis showed that microbial exposure affected both bronchoalveolar lavage fluid and plasma metabolomes, suggesting systemic effects of microbial exposure on the organism. Differences in the structure of artificial microbiota had inconsistent effects on both the baseline state and the post-infection state, hinting at crosstalk between microbial exposure and Klebsiella pneumoniae infection. KEGG pathway analysis unveiled possible molecular mechanisms underlying the overall impact of microbial exposure on the lungs and the body as a whole. In the intestinal microbiota, differences were found in composition at the phylum and genus levels. Spearman correlation analysis established potential correlations between intestinal microbiota and differential metabolites, suggesting a potential link within the lung-gut axis. CONCLUSION: This study demonstrated the significant and systemic impact of air microbiota structure differences on health. Future research should explore the underlying mechanisms to enhance our understanding of the air-environment-health relationship and identify interventions for improving public health strategies.