Integrating Metabolomics and Gut Microbiota to Reveal the Therapeutic Effect of Lonicerae japonicae Flos Against Respiratory Syncytial Virus.

Objectives: This study aimed to investigate the therapeutic effects and potential mechanisms of Lonicerae japonicae Flos (Jinyinhua, JYH) against respiratory syncytial virus (RSV)-induced pneumonia by integrating lung tissue metabolomics with gut microbiota analysis. Methods: An RSV-infected mouse model was established through intranasal inoculation. Lung pathological changes, viral RNA levels, lung index, and inflammatory cytokine levels were evaluated. Untargeted metabolomics and 16S rRNA gene amplicon sequencing were performed to characterize JYH-mediated alterations in pulmonary metabolites and the gut microbiota. Spearman correlation analysis was conducted to assess associations between differentially abundant bacterial genera and significantly altered metabolites. Results: JYH alleviated RSV-induced pulmonary histopathological injury, reduced viral RNA levels, decreased lung index and interleukin-6 (IL-6) levels, and increased interferon-γ (IFN-γ) levels. Metabolomic profiling identified 46 differential metabolites, among which 26 showed a reversal trend following JYH administration. These metabolites were mainly enriched in pathways associated with the synaptic vesicle cycle, lysosomal function, and Forkhead box O (FoxO) signaling. Gut microbiota analysis showed that JYH increased microbial richness and diversity, whereas KEGG-based functional prediction indicated that the differentially abundant taxa were primarily involved in amino acid, carbohydrate, and nucleotide metabolism. Moreover, correlation analysis revealed significant associations between key bacterial genera, including Gemella, Sutterella, and CC_115, and differential metabolites such as pyridoxamine, uridine monophosphate (UMP), and argininosuccinic acid. Conclusions: JYH may protect against RSV-induced pneumonia by restoring pulmonary metabolic homeostasis and modulating gut microbiota composition. These findings provide new insights into metabolite-microbiota interactions underlying the anti-RSV activity of JYH.