Plasma concentrations of short-chain fatty acids in COPD patients and healthy controls: Exploring the gut-microbiota link

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Background: Microbiota-derived metabolites, particularly short-chain fatty acids (SCFAs), may influence disease development by modulating the immune system. This study examined whether COPD was related to circulating SCFA concentrations. Methods: We included 130 COPD patients and 103 controls in a single-centre case-control study at Haukeland University Hospital, Norway, 2013-2015. Eight SCFAs (α-methylbutyrate, valerate, propionate, isovalerate, isobutyrate, formate, butyrate, and acetate) were quantified in plasma using isotope-labelled gas chromatography-tandem mass spectrometry. Body composition was assessed by bioelectrical impedance analysis of fat and fat-free mass. Regression analyses of log-transformed SCFA levels were used to evaluate associations with COPD, unadjusted and adjusted for age, sex, smoking, and body composition. Results: The COPD patients and controls were well-matched in age and sex but differed in smoking status (0% never-smoker in COPD vs. 18% in controls). COPD patients were more prone to cachexia (21% vs. 9.8% in controls). Overall, plasma acetate concentrations were highest (geometric mean (SD) 35.62 (2.01) µmol/L), followed by formate (12.05 (1.43) µmol/L); other SCFAs were < 1 µmol/L. Plasma formate concentrations were inversely associated with COPD status (OR [95% CI]: 0.37 [0.18–0.71], p = 0.005; adjusted OR [95% CI]: 0.33 [0.15–0.65], p < 0.004). Other SCFAs showed no significant association (p > 0.05). Smoking was significantly associated with COPD status (p < 0.001), while body composition was not (p > 0.05). Conclusions: The SCFA formate was inversely related to COPD. Further research exploring underlying mechanisms is warranted.

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