Impact of Butyrate on Small and Large Airways: Effects on Cell Viability, Inflammatory Changes and Permeability

Abstract

Chronic airway diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and asthma pose a significant global health burden. The pathophysiology involves chronic inflammation, with oxidative stress playing a crucial role in disease severity. Current treatments, especially for COPD, have limitations, necessitating exploration of alternative therapeutic approaches. In this study, we investigated the potential effects of butyrate, a short-chain fatty acid, on airway epithelial cells. Human bronchial epithelial cells (BEAS-2B) and bronchiolar epithelial carcinoma cells (A549) were cultured and exposed to hydrogen peroxide (H2O2) to induce oxidative stress. Butyrate was then applied at various concentrations, and the impact on cell viability, epithelial permeability, inflammatory cytokines, and gene expression was assessed. Our cell viability experiments revealed a dose-dependent reduction in viability with H2O2, while butyrate was found to be safe as it did not affect cell viability. Additionally, butyrate showed decrease in small airway permeability. Butyrate demonstrated anti- inflammatory properties, suppressing H2O2-induced release of interleukin (IL)-6, IL-8, and granulocyte macrophage colony-stimulating factor (GM-CSF) in large airways. Gene expression analysis further highlighted complex regulatory effects of butyrate on inflammatory pathways. Our study suggests that butyrate may have potential therapeutic benefits in chronic airway diseases by modulating inflammation, permeability, and gene expression. However, further research, including in vivo studies and exploration of endogenous butyrate utilization, is needed to fully understand its pharmacodynamics and clinical relevance. Our findings contribute to the understanding of short-chain fatty acids as potential candidates for respiratory disease treatment.