Fuzheng Jiedu Formula Ameliorates Acute Lung Injury by Modulating Gut Microbiota to Enhance Short-Chain Fatty Acid

Aim of Study: The objective of this research is to clarify the mechanism by which FZJDF mitigates lipopolysaccharide (LPS)- ALI through the enhancement of short-chain fatty acids (SCFAs) production by Clostridium butyricum ( C. butyricum ), and the modulation of the gut microbiota-gut-lung axis. Materials and Methods: The mice were treated with FZJDF for 7 days and then treated with LPS. The therapeutic efficacy of FZJDF against LPS-induced ALI was evaluated through lung-to-weight ratio, Inflammatory factor, pathological changes. Additionally, the intestinal barrier function was evaluated by analyzing tight junction protein expression levels. 16S rRNA gene sequencing was employed to monitor alterations in the intestinal microbiome and pulmonary microbiota, while gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography (UPLC) were utilized to quantify the concentrations of SCFAs. Ultimately, the necessity of C. butyricum for FZJDF’s therapeutic influence was confirmed through antibiotic-mediated gut microbiota depletion. Results: FZJDF significantly decreased lung-to-weight ratio and reducing inflammatory cell infiltration of neutrophils. Furthermore, it significantly elevated the expression levels of tight junction proteins. It is plausible that FZJDF may improve intestinal and lung microecological imbalance and stimulate the synthesis of SCFAs. Notably, we determine C. butyricum as the crucial bacterium for the role of FZJDF in gut barrier repair and suppression of lung inflammation in ALI mice. The use of antibiotics led to the repair of the intestinal barrier and a failure in SCFAs production, whereas C. butyricum colonization restores the therapeutic effect of FZJDF in ALI mice, further confirming that FZJDF attenuates ALI. Conclusion: Our results imply that FZJDF could exert its palliative effect in ALI by regulating the intestinal microbiota to increase the production of SCFAs, which in turn inhibits neutrophil-mediated inflammatory responses. These findings support microbiota-targeted traditional medicine as a translational strategy for acute lung injury. Keywords: fuzhengjiedu formula, LPS-induced ALI, short-chain fatty acids, gut-lung axis