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Data and code from: Plasma short-chain fatty acids are associated with COPD and COPD phenotypes

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Jun 10, 2026 version files 91.98 KB

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Abstract

Short-chain fatty acids (SCFAs) are metabolites produced by gut microbiota and may influence COPD development by modulating the immune system. This study examined the relationship between circulating SCFA concentrations and COPD and COPD phenotypes. We report findings from a single-centre case-control study with 130 COPD patients and 103 controls. Eight SCFAs (α-methylbutyrate, valerate, propionate, isovalerate, isobutyrate, formate, butyrate, and acetate) were quantified in plasma using isotope-labelled gas chromatography-tandem mass spectrometry. Associations between SCFAs, COPD status, and COPD phenotypes (severely obstructive COPD, emphysema, eosinophilic COPD, frequent exacerbations, and symptom burden) were evaluated using multivariable regression analyses adjusted for age, sex, smoking, and body composition. Plasma formate concentrations were inversely associated with COPD status (adjusted OR 0.33; 95 % CI 0.15 to 0.66; p = 0.004). Propionate and isobutyrate concentrations were inversely associated with severely obstructive COPD (adjusted ORs 0.46; 95 % CI 0.24 to 0.86; p = 0.018, and 0.33; 95 % CI 0.14 to 0.75; p = 0.012, respectively). Propionate concentrations were also inversely associated with frequent exacerbations of COPD (adjusted OR 0.23; 95 % CI 0.07 to 0.62; p = 0.007). Isovalerate was positively associated with symptom burden (CAT score) (estimate 1.76; 95 % CI 0.20 to 3.32; p = 0.027). No consistent associations were observed for emphysema or eosinophilic COPD. SCFA formate was inversely related to COPD. Several SCFAs were associated with specific COPD phenotypes. Future studies should investigate the underlying mechanisms linking SCFAs to COPD and include the often-overlooked formate, while acknowledging formate’s dual origin.