Acarbose reduces Pseudomonas aeruginosa respiratory tract infection in type 2 diabetic mice

Abstract

Background Type 2 diabetes mellitus (T2DM) is widely prevalent worldwide, and respiratory tract infections have become the primary cause of death in T2DM patients who develop concurrent infections. Among these, Pseudomonas aeruginosa infection has been found to exhibit a high mortality rate and poor prognosis and is frequently observed in bacterial infections that are concurrent with COVID-19. Studies have suggested that acarbose can be used to treat T2DM and reduce inflammation. Our objective was to explore the effect of acarbose on P. aeruginosa respiratory tract infection in T2DM individuals and elucidate its underlying mechanism. Methods High-fat diet (HFD) induction and P. aeruginosa inhalation were used to establish a respiratory tract infection model in T2DM mice. The effect and mechanism of acarbose administered by gavage on P. aeruginosa respiratory tract infection were investigated in T2DM and nondiabetic mice using survival curves, pathological examination, and transcriptomics. Results We found that P. aeruginosa respiratory tract infection was more severe in T2DM mice than in nondiabetic individuals, which could be attributed to the activation of the NF-κB and TREM-1 signaling pathways. When acarbose alleviated P. aeruginosa respiratory tract infection in T2DM mice, both HIF-1α and NF-κB signaling pathways were inhibited. Furthermore, inhibition of the calcium ion signaling pathway and NF-κB signaling pathway contributed to the attenuation of P. aeruginosa respiratory tract infection by acarbose in nondiabetic mice. Conclusions This study confirmed the attenuating effect of acarbose on P. aeruginosa respiratory tract infections in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.