Association between dietary fibre, microbial metabolites and airway obstruction in COPD patients and murine models

Introduction: The gut microbiome regulates lung immune responses through production of short chain fatty acids (SCFAs) by fermentation of dietary fibre. Aims and objectives: We hypothesised that dietary fibre and SCFAs reduce airway obstruction in COPD. We aimed to characterise the relationship between fibre intake, SCFAs and airway obstruction in COPD patients and a murine model of COPD. Methods: COPD patients (n=43) were assessed for lung function (spirometry) and fibre intake (dietary questionnaire). Mice were fed a high fibre diet or received SCFAs in drinking water and were exposed to cigarette smoke (12 weeks). Histopathology (collagen deposition, epithelial thickening) and lung function (Flexivent) were assessed. Faecal SCFAs (COPD patients and mice) were quantified by liquid chromatography-mass spectrometry. Results: COPD patients with the lowest fibre intake (stratified by quartiles) had lower FEV1, FEV1/FVC, and mean expiratory flow between 25% and 75% FVC (MEF25-75) (p<0.05 vs. highest quartile). Faecal SCFAs were positively correlated with FEV1/FVC (r = 0.36; p<0.05) and MEF25-75 (r = 0.47; P<0.01). In mice, a high fibre diet increased faecal SCFAs and alleviated cigarette smoke-induced increases in collagen deposition, epithelial thickening and central airway resistance (p<0.05 vs. control diet). SCFAs in drinking water replicated these effects. Conclusion: High fibre intake and faecal SCFAs were associated with better lung function in COPD patients and murine models of COPD, suggesting dietary interventions may assist patients to preserve their lung function.