Vancomycin protects against acute respiratory distress syndrome by promoting butyrate metabolism

Abstract

Abstract Background Acute respiratory distress syndrome (ARDS) represents a clinical syndrome featuring refractory hypoxemia. Several reports have identified the role of the gut microbiota in affecting the immune activity and pathological characteristics of respiratory disorders via the gut-lung axis. However, the precise metabolic mechanism remains unknown. The present work focused on investigating the processes by which gut microbiota influence ARDS and identifying potential therapeutic targets of ARDS. Methods The feces and serum samples of 23 ARDS patients were collected, and a lung injury model was generated by transplanting microbiota from ARDS patients into healthy C57BL/6J mice. The changes in the gut microbiota and metabolic phenotypes of the feces samples from ARDS patients and lung-injured mice were analyzed using 16sRNA sequencing technology and metabolomics based on 1H nuclear magnetic resonance (NMR), respectively. The effect of gut microbiota on ARDS was also explored after giving an oral vancomycin treatment to lung-injury mice. Further, enzyme-linked immunosorbent assay (ELISA) was used to evaluate the hyperinflammatory response in mice and intestinal permeability in ARDS patients. Additionally, qRT-PCR and staining were performed to analyze colonic barrier function and permeability. Results Firmicutes formed the vital species of microbiota that was different in lung-injury mice. Moreover, butyrate (produced by Firmicutes) was the most crucial metabolite in the feces samples of ARDS patients and lung-injury mice. Elisa and HE results showed aggravated functional disturbances in the intestinal barrier of ARDS patients and lung inflammation in the lung-injured mice. These phenomena were significantly alleviated after the oral administration of vancomycin. Besides, the utilization of butyrate in the colon of mice was increased considerably. The level of butyrate was reduced in the feces but increased in the colon. Conclusions Thus, vancomycin affects butyrate metabolism in the colon by influencing the gut microbiota. Modulating colonic butyrate metabolism could help treat ARDS.