Yinhua Pinggan Granules alleviate lung and intestinal damage in influenza virus-infected mice by modulating gut microbiota and its metabolites to activate the GPR43-MAVS-IRF3-IFN-β pathway.

Objective: Derived from Ma Huang Decoction in the Methods: Using a mouse model disrupted by a four-antibiotic regimen, we assessed survival, weight, lung, and spleen indices post-IAV infection. We evaluated lung and intestinal pathology, viral load, and protein expressions via H&E staining, RT-qPCR, and immunofluorescence. 16S rRNA sequencing and targeted metabolomics were utilized to uncover the impact of YHPG treatment on disrupted gut microbiota and its metabolites after H1N1 infection. Results: H&E staining showed severe lung and intestinal damage in IAV-infected mice with disrupted gut microbiota. Immunofluorescence results demonstrated that relative depletion of gut microbiota might exacerbate colonic barrier damage in IAV-infected mice. YHPG restored microbiota diversity, increasing SCFA-producing bacteria, aligning with metabolite changes. Western blot and RT-qPCR showed activation of the GPR43-MAVS-IRF3-IFN-I pathway, linked to SCFA regulation. Conclusion: YHPG alleviate influenza symptoms, promoting SCFA-producing bacteria and maintaining gut homeostasis. They modulate the GPR43-MAVS-IRF3-IFN-β pathway, suggesting novel treatment avenues for influenza through gut microbiota modulation.