Modulation of the gut-lung axis by probiotic VSL#3 alleviates acute lung injury via restricting NETosis in sepsis

Acute lung injury (ALI), frequently occurring as an early complication of sepsis, results from pulmonary involvement in systemic inflammation and immune dysregulation. During the onset of sepsis, neutrophils release neutrophil extracellular traps (NETs) to combat infection; however, excessive NETs formation exacerbates lung injury in later stages. In this study, a murine model of cecal ligation and puncture (CLP)-induced ALI was employed. We observed gut microbiota disruption via 16S rRNA sequencing, accompanied by substantial neutrophil infiltration in lung tissue and bronchoalveolar lavage fluid (BALF), alongside elevated NETs levels in the lung, BALF, and plasma. Inflammatory cytokines (IL-1β, TNF-α, and IL-6) were also markedly increased in plasma and lung tissue. Mice pretreated for one week with the probiotic VSL#3 prior to CLP exhibited a remodeled gut microbiota in terms of abundance and composition compared to CLP-only mice. Furthermore, probiotic pretreatment mitigated inflammatory responses and lung injury, reduced neutrophil infiltration, and decreased NETs release. In conclusion, gut microbiota modulates pulmonary inflammation in CLP-induced ALI by limiting neutrophil infiltration and NETs release. Probiotic supplementation may represent a promising therapeutic strategy for ameliorating ALI.