Highly diverse sputum microbiota correlates with the disease severity in patients with community-acquired pneumonia: a longitudinal cohort study

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Abstract
Background: Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis. Methods: We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced. Results: The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections. Conclusion: Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.
Funding Information
  • National Natural Science Foundation of China (32100098)
  • Beijing Nova Program (Z211100002121135, Z191100006619102)
  • Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-038)
  • Fundamental Research Funds for the Central Universities (3332021092)
  • Fondation Mérieux
  • National Key R&D Program of China (2022YFA1304300)
  • non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2019PT310029)
  • Beijing Municipal Natural Science Foundation of China (Z190017)

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