Mangiferin improves Acinetobacter baumannii-induced pneumonia by modulating M1/M2 macrophage polarization and the gut microbiota.

Acinetobacter baumannii is a major cause of hospital-acquired pneumonia, posing a serious challenge to clinical therapy due to its high antibiotic resistance. Host-directed approaches using bioactive compounds with immunomodulatory properties may provide an alternative strategy for preventing A. baumannii-induced pulmonary inflammation. Mangiferin, a natural polyphenolic compound, has demonstrated anti-inflammatory properties in various models, but its role in A. baumannii-induced pneumonia remains unexplored. In this study, we established a murine model of A. baumannii-induced pneumonia to evaluate the prophylactic effects of mangiferin. Pretreatment with mangiferin significantly alleviated pulmonary pathological damage and reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), with concomitant decreases in the expression of proteins associated with TLR4/MyD88/NF-κB signaling. Additionally, mangiferin pretreatment was associated with lower levels of the M1 macrophage marker CD86 and higher levels of the M2 macrophage marker CD206, suggesting an association with altered alveolar macrophage polarization. Moreover, mangiferin pretreatment was accompanied by alterations in gut microbiota composition, including higher relative abundances of Lactobacillus and Alloprevotella and lower relative abundances of inflammation-associated taxa, including Luxibacter and Eubacterium_J. Collectively, these findings demonstrate the prophylactic effects of mangiferin against A. baumannii-induced pneumonia in mice and indicate that these effects are associated with alterations in pulmonary inflammatory responses, macrophage polarization-related markers, and gut microbiota composition. Further interventional studies are required to establish the causal contributions of these changes to the protective effects of mangiferin.