Post-COVID-19 disruption of the respiratory microbiome modulates Mycoplasma pneumoniae: a multi-center retrospective...

Area of Science:

• Microbiology
• Infectious Diseases
• Computational Biology

Background:

• A resurgence of Mycoplasma pneumoniae pneumonia (MPP) in children has been observed post-COVID-19 pandemic, with increased disease severity.
• The underlying reasons for this increased severity, particularly shifts in the respiratory microbiota, remain poorly understood.
• Understanding these microbial shifts is crucial for managing post-pandemic respiratory infections.

Purpose of the Study:

• To investigate how pandemic-related disruptions in the respiratory microbiota influence the severity of Mycoplasma pneumoniae pneumonia (MPP).
• To identify specific microbial communities and their roles in regulating M. pneumoniae colonization and disease progression.
• To develop predictive models for MPP severity based on microbial composition.

Main Methods:

• Analysis of multiple independent patient cohorts to assess respiratory microbiota composition.
• Identification of microbial modules associated with M. pneumoniae colonization and disease severity.
• Utilized a Susceptible-Infected-Recovered (SIR) model to simulate infection dynamics under varying microbiota conditions.
• Developed a machine-learning model incorporating eight key microbial species to predict MPP cases and severity.

Main Results:

• Depletion of protective respiratory microbiota was found to exacerbate MPP severity by compromising colonization resistance against M. pneumoniae.
• Two distinct antagonistic microbiota modules, differing in metabolic features and community structure, were identified as key regulators of pathogen colonization and disease.
• The machine-learning model effectively differentiated between infected individuals and controls and predicted infection severity.
• Simulations using the SIR model provided insights into M. pneumoniae infection dynamics influenced by different microbiota states.

Conclusions:

• The respiratory microbiota plays a critical role in determining the severity of Mycoplasma pneumoniae infections.
• Disruptions to the respiratory microbiota, particularly depletion of protective members, contribute significantly to increased MPP severity.
• Findings provide a framework for managing post-pandemic respiratory infections by targeting microbial community dynamics.
• Restoring or enhancing protective microbiota may represent a viable therapeutic strategy for MPP and other respiratory infections.