Sputum short-chain fatty acids, microbiome, inflammation, and mucus plugging in obstructive airway disease.

Abstract

Background: Short-chain fatty acids (SCFAs), produced by anaerobic bacteria through fermentation in the gut, may suppress eosinophilic inflammation while potentially promoting neutrophilic inflammation. However, the role of local SCFAs in airway microbiome, inflammation, and mucus plugging in type 2 dominant obstructive airway diseases remains unclear.

Objective: To investigate associations between sputum SCFAs and the relative abundance of anaerobic bacteria, neutrophil and eosinophil counts in sputum, and mucus plug scores on computed tomography (CT) in patients with obstructive airway diseases.

Methods: Sputum samples and chest CT were prospectively collected in stable patients with asthma with fixed airflow limitation, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO). Sputum samples were analyzed for SCFAs concentrations, including n-butyrate, acetate, and propionate, microbiome composition using 16S rRNA sequencing, and inflammatory cell differentials.

Results: In 46 patients, enriched for ACO with relatively high type 2 markers, higher SCFA levels were associated with higher relative abundance of phylum Bacteroidetes and lower relative abundance of phylum Proteobacteria. Hierarchical clustering identified a severe eosinophil-dominant inflammation cluster characterized by lower SCFAs levels and higher mucus plug scores. In the two neutrophilic clusters, one characterized by higher SCFAs levels and the other by lower SCFAs levels, lower butyrate levels were significantly associated with higher mucus plug scores.

Conclusion: Local SCFA concentrations may be closely associated with the airway microbiome and influence mucus plugging in ACO-enriched populations. Understanding these interactions could inform therapeutic strategies targeting SCFAs or the microbiome to manage type 2 dominant obstructive airway diseases.