Gut microbiota and pneumonia From health to severe infection

This thesis investigates the composition and impact of human microbiota throughout the continuum of health to severe pneumonia, in order to decipher the role and targetability of the microbiome in infection susceptibility, severe illness and its recovery. Despite the recent surge in research on the role of gut microbiota in enteric infections, current understanding on the role of microbiota during pneumonia in humans is limited, and no microbiota-targeted therapies have been implemented in everyday management. We hypothesised that the gut microbiota - particularly obligate anaerobic butyrate-producing bacteria - play a protective role against systemic infections in healthy individuals, are distorted during pneumonia and its recovery, safeguard against adverse clinical outcomes in hospitalised patients, and represent a treatable trait. We used general population cohorts, cohorts of hospitalised patients (including during their recovery), and murine models of pneumonia to examine the role of microbiota before, during and following pneumonia. Our findings show that gut and lung microbiota are altered during hospital admission for pneumonia, and correlate with clinical outcomes. Gut microbiota alterations precede hospitalisation and are associated with infection susceptibility, but also remain altered following recovery. Finally, we describe strategies to target gut microbiota to improve outcomes during pneumonia. Overall, this work advances our understanding of the role of gut microbiota in pneumonia, and its potential as preventive and therapeutic target.