Gut dysbiosis in early severe burns contributes to acute lung injury by impairing neutrophil chemotaxis

Severe burns complicated by acute lung injury are critical causes of respiratory failure and multiple organ dysfunction syndrome. Neutrophils extensively infiltrate lung tissues early postburn to mediate pulmonary damage, but the underlying mechanisms remain unclear. We analyzed gut microbiota of severe burn patients via metagenomics and metabolomics, assessed neutrophil chemotaxis using a self-developed in vitro agarose model, and validated Faecalibacterium prausnitzii and butyrate's effects on restoring neutrophil chemotaxis in gut microbiota-depleted mice via oral gavage (plus in vivo validation with small animal imaging). Bronchoalveolar lavage fluid biomarkers and pulmonary function tests evaluated pulmonary injury from impaired neutrophil chemotaxis. Early postburn, F. prausnitzii and its metabolite butyrate were significantly depleted in patients, concurrent with impaired neutrophil chemotaxis-restored by butyrate supplementation. In murine burn models, F. prausnitzii or butyrate rescued neutrophil chemotaxis, reduced pulmonary neutrophil infiltration, and attenuated lung injury. Mechanistically, butyrate restored neutrophil function in a severe burn patient plasma-stimulated model by downregulating P2X1 receptor expression and suppressing myosin light chain phosphorylation. Our findings indicate postburn gut microbiota dysbiosis and metabolite alterations disrupt neutrophil chemotaxis, causing excessive pulmonary neutrophil infiltration/activation. This highlights gut microbiota-derived metabolites as potential therapeutics for mitigating neutrophil-driven lung injury early postsevere burns.