ERP011871 PRJEB10599 qiime_ppdid_538 qiime_ppdid_538 Worgall Angenent Mice Lung Study Diseases that favor colonization of the respiratory tract with P. aeruginosa, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), are characterized by an altered airway microbiome. Chronicity and virulence of P. aeruginosa respiratory tract infections is likely influenced by interactions with other lung microbiota or their products. The bacterial fermentation product 2,3-butanediol enhances virulence and biofilm formation of P. aeruginosa in vitro. This study assesses the effects of 2,3-butanediol on P. aeruginosa virulence in vivo and on microbiome in lung tissues. P. aeruginosa grown in the presence of 2,3-butanediol and encapsulated in agar beads persisted longer in the murine respiratory tract and resulted in increased colonization of the lung by environmental microbes such as Turicibacter, Clostridium and Parabaceroides. This suggests a role of fermentation products from the lung microbiota on P. aeruginosa virulence and aptitude to colonize the respiratory tract, resulting in dynamic shifts in microbiota diversity and disease susceptibility. Diseases that favor colonization of the respiratory tract with P. aeruginosa, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), are characterized by an altered airway microbiome. Chronicity and virulence of P. aeruginosa respiratory tract infections is likely influenced by interactions with other lung microbiota or their products. The bacterial fermentation product 2,3-butanediol enhances virulence and biofilm formation of P. aeruginosa in vitro. This study assesses the effects of 2,3-butanediol on P. aeruginosa virulence in vivo and on microbiome in lung tissues. P. aeruginosa grown in the presence of 2,3-butanediol and encapsulated in agar beads persisted longer in the murine respiratory tract and resulted in increased colonization of the lung by environmental microbes such as Turicibacter, Clostridium and Parabaceroides. This suggests a role of fermentation products from the lung microbiota on P. aeruginosa virulence and aptitude to colonize the respiratory tract, resulting in dynamic shifts in microbiota diversity and disease susceptibility.