Study on the Mechanism of Qingfei Litan Formula in Improving Acute Lung Injury in Mice by Regulating Gut Microbiota and Short-chain Fatty Acids Metabolism

OBJECTIVE  To analyze the characteristics of gut microbiota in mice with acute lung injury and the intervention effect of Qingfei Litan Formula, to explore the correlation between changes in gut microbiota and lung inflammation, oxidative stress, and short-chain fatty acids(SCFAs) metabolism, thereby revealing the mechanism of action of Qingfei Litan Formula.

METHODS  The acute lung injury(ALI) mouse model was established via lipopolysaccharide(LPS) tracheal instillation after administering different doses of Qinglong Lipophlegm Formula. After euthanasia, we evaluated inflammatory cells and factors in broncho-alveolar lavage fluid(BALF) examined lung pathology, calculated the lung coefficient and wet/dry ratio, assessed oxidative stress markers in lung tissues, measured short-chain fatty acids(SCFAs) levels in serum, and conducted 16S rRNA sequencing of the intestinal microbiota.

RESULT  Qingfei Litan Formula alleviated alveolar damage and pulmonary edema in ALI mice, reduced inflammatory cells and factors in BALF, decreased malondialdehyde in lung tissue, increased superoxidedismutase and glutathione peroxidase activities, and elevated SCFAs in blood. It enhanced gut microbiota diversity, increased beneficial bacteria like Lachnospiraceae NK4A136, Lactobacillus , Prevotellaceae UCG-001, Prevotellaceae NK3B31, Ruminiclostridium 6, Enterorhabdus, Ruminococcaceae UCG-013, and decreased harmful bacteria like Alloprevotella, Erysipelatoclostridium, Peptococcus. Beneficial genera were negatively correlated with pulmonary inflammation and oxidative stress, and positively with acetic, propionic, and butyric acids in blood. Harmful genera showed opposite correlations. Acetic, propionic, and butyric acids were negatively correlated with inflammatory factors and oxidative stress in BALF, while pentanoic acid was negatively correlated with IL6 and TNF-α levels.

CONCLUSION  Qingfei Litan Formula may exert anti-inflammatory and anti-oxidative stress effects by regulating gut microbiota and SCFAs metabolism, thereby protecting lung tissue in ALI mice.