Cystic fibrosis restricts systemic and local lipid modulation during lung infection

Cystic fibrosis (CF) is an inherited disorder associated with respiratory dysfunction due to the reduced airway surface hydration and muco-obstruction of the airways, which is also associated with compromised lipid composition of sputum. Altered pulmonary homeostasis can result in chronic infections with treatment-resistant respiratory pathogens, such as multi-drug-resistant Pseudomonas aeruginosa . Changes in dietary fatty acids can influence respiratory function by altering mucus viscosity. However, the efficacy of such dietary approaches may be affected by the hepato-biliary complications commonly experienced by CF patients. Interestingly, bacterial infections in the lung can also influence lipid metabolism in the liver. In this study we sought to delineate the influence of infection and diets enriched with lard versus fish oil on lipid speciation in distinct niches, and their influence on lung and liver function in a Sprague-Dawley rat model of CF. As expected, the dietary intervention induced distinct shifts in host lipid profiles, including higher abundances of ω-3 fatty acids in fish oil fed animals; however, the magnitude of these increases in circulation was greater in wild-type (WT) rats than in CF rats. Similarly, infection-induced lipid changes were prominent in WT animals, with fewer changes observed in CF mutant animals. Diet did not influence liver function in our study, but rather, even 3 weeks after P. aeruginosa challenge, infected animals demonstrated mild liver damage, which was at a similar level between WT and CF rats. In regard to respiratory function, infection was associated with increased elastance and reduced compliance across groups. However, dietary fatty acid modification did not significantly alter baseline lung mechanics, nor modify the mechanical response to infection in CF animals. This study advances our understanding of CF lipid biology in the context of diet and infection, which are core facets of CF disease complications.