Faecalibacterium prausnitzii ameliorates sepsis-induced acute lung injury via gut-lung axis by regulating arachidonic acid-LXA4-Nrf2-HO-1 pathway and restoring gut microecology

Introduction Sepsis-induced acute lung injury (S-ALI) is a life-threatening condition in intensive care units. The gut-lung axis has recently emerged as an important regulator of pulmonary inflammation. However, the role of Faecalibacterium prausnitzii ( F. prausnitzii ) in S-ALI remains unclear. Methods In this study, 16S rRNA high-throughput sequencing revealed significant gut microbiota dysbiosis in S-ALI patients, characterized by a markedly reduced relative abundance of F. prausnitzii . Moreover, the depletion of this probiotic was associated with increased clinical inflammatory indices and disease severity. Subsequently, the effects of F. prausnitzii strain intervention on S-ALI were investigated in two S-ALI murine models, including cecal ligation puncture (CLP) and lipopolysaccharide (LPS)-induced models. Results We found that F. prausnitzii intervention significantly attenuated acute lung injury in sepsis by reducing inflammation and oxidative stress. Importantly, F. prausnitzii treatment restored gut microbial homeostasis by enhancing intestinal barrier integrity and increasing the production of short-chain fatty acids (SCFAs), particularly butyrate. Mechanistically, non-targeted metabolomics analysis revealed that the protective effects of F. prausnitzii may be associated with the modulation of arachidonic acid (AA) metabolism, accompanied by increased levels of the anti-inflammatory mediator lipoxin A4 (LXA4). In addition, the expression of Nrf2 and HO-1 was upregulated in the intervention group, suggesting a potential involvement of the LXA4-Nrf2-HO-1 signaling pathway. Correlation analysis further indicated complex interactions among gut microbiota, SCFAs, metabolomic profiles, and inflammatory and oxidative stress-related factors following F. prausnitzii intervention. Discussion Collectively, F. prausnitzii ameliorates the progression of S-ALI by restoring gut microecology and may be associated with AA metabolism and oxidative stress-related pathways, which may contribute to a potential therapeutic strategy targeting the gut-lung axis and AA metabolic pathways.