TY - JOUR T1 - Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth JF - European Respiratory Journal JO - Eur Respir J SP - 1033 LP - 1045 DO - 10.1183/09031936.00143614 VL - 46 IS - 4 AU - Peyman Ghorbani AU - Prisila Santhakumar AU - Qingda Hu AU - Pascal Djiadeu AU - Thomas M.S. Wolever AU - Nades Palaniyar AU - Hartmut Grasemann Y1 - 2015/10/01 UR - http://erj.ersjournals.com/content/46/4/1033.abstract N2 - The hypoxic environment of cystic fibrosis airways allows the persistence of facultative anaerobic bacteria, which can produce short-chain fatty acids (SCFAs) through fermentation. However, the relevance of SCFAs in cystic fibrosis lung disease is unknown. We show that SCFAs are present in sputum samples from cystic fibrosis patients in millimolar concentrations (mean±sem 1.99±0.36 mM).SCFAs positively correlated with sputum neutrophil count and higher SCFAs were predictive for impaired nitric oxide production. We studied the effects of the SCFAs acetate, propionate and butyrate on airway inflammatory responses using epithelial cell lines and primary cell cultures. SCFAs in concentrations present in cystic fibrosis airways (0.5–2.5 mM) affected the release of granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and interleukin (IL)-6. SCFAs also resulted in higher IL-8 release from stimulated cystic fibrosis transmembrane conductance regulator (CFTR) F508del-mutant compared to wild-type CFTR-corrected bronchial epithelial cells. At 25 mM propionate reduced IL-8 release in control but not primary cystic fibrosis epithelial cells. Low (0.5–2.5 mM) SCFA concentrations increased, while high (25–50 mM) concentrations decreased inducible nitric oxide synthase expression. In addition, SCFAs affected the growth of Pseudomonas aeruginosa in a concentration- and pH-dependent manner.Thus, our data suggest that SCFAs contribute to cystic fibrosis-specific alterations of responses to airway infection and inflammation.Short-chain fatty acids contribute to CF-specific alterations of responses to airway infection and inflammation http://ow.ly/L7ZI9 ER -