Chronic lung inflammation is the major driver of disease pathogenesis in patients with cystic fibrosis
(CF) and chronic obstructive pulmonary disease (COPD). Available anti-inflammatory agents are
ineffective in both patient populations, emphasizing the need to explore radically novel therapeutic
avenues. The lungs of patients with CF and COPD are colonized by a wide collection of
microorganisms (microbiome) which contains both bacteria considered as pathogenic and nonpathogenic
(commensal). Recent studies reported a negative correlation between the presence of
specific commensal microbiome bacteria (including Rothia mucilaginosa) and lung inflammation in
CF patients. Our preliminary in vitro data confirmed an anti-inflammatory effect of R. mucilaginosa.
Hence, this project will use these promising data to evaluate the therapeutic potential of R.
mucilaginosa. To this end, we will confirm the anti-inflammatory effect of R. mucilaginosa in
complex and physiologically relevant in vitro models of CF and COPD lung inflammation, as well as in
in vivo mouse models. The anti-inflammatory compound(s) produced by this bacterium will be
identified and the mode of action unveiled. Finally, the anti-inflammatory effect of R. mucilaginosa
will be validated in a CF and COPD patient cohort. Not only can this project lead to the discovery of
novel microbial products with anti-inflammatory characteristics, it has the potential to result in a
paradigm-shift for the treatment of CF and COPD.