Abstract
Multidrug-resistant Pseudomonas aeruginosa (MDR-PA) pneumonia is characterized by limited clinical antimicrobial options, severe inflammatory damage and high mortality. MDR-PA infection can trigger intestinal microecological imbalance and immune disorders. Qiguiyin Formula is a classic traditional Chinese medicinal compound clinically applied for infections caused by drug-resistant Pseudomonas aeruginosa. This study aimed to clarify the relationship between intestinal flora dysbiosis induced by MDR-PA infection and pathological injuries in the lung and intestine, as well as evaluate the therapeutic potential of Qiguiyin Formula combined with fosfomycin, and further elaborate its mechanism of action from the perspective of the gut-lung axis.Methods
Mouse models of multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection and corresponding intervention models treated with Qiguiyin Formula and fosfomycin were established. HE staining, RT-qPCR, chemiluminescence immunoassay, 16S rRNA sequencing and non-targeted metabolomics analysis were applied to assess immune damage and gut microbiota structure in lung and intestinal tissues.Results
MDR-PA infection leads to severe imbalance of the intestinal flora, manifested by an increase in pathogenic bacteria (Escherichia coli, Shigella) and a significant decrease in beneficial bacteria (Lactobacillus, Bifidobacterium), and an increase in inflammatory metabolites such as arachidonic acid, linoleic acid, and α-linolenic acid, causing disorders in lipid metabolism pathways and MAPK signaling pathways. The HE staining results show that MDR-PA infection damages the lung structure, triggers alveolar inflammation, downregulates the expression of ZO-1, damages the colonic barrier, and induces a pro-inflammatory cytokine storm, resulting in a high mortality rate. In terms of treatment, the intervention of the Qiguiyin Formula combined with fosfomycin demonstrates the advantages of a synergistic effect: improving the imbalance of intestinal flora, reshaping core metabolic pathways such as lipids, amino acids, and arginine, repairing the integrity of the intestinal barrier, and inhibiting the expression of inflammatory factors.Conclusion
MDR-PA infection disrupts intestinal flora homeostasis and induces metabolic disorders. The combined use of Qiguiyin Formula and fosfomycin alleviates pulmonary injury by improves the diversity and stability of the intestinal microbiota, corrects the abnormal activation of lipid and amino acid metabolic pathways, and restores the normal metabolic signals of the microbiota, thereby inhibiting lung damage.