Sheng Jiangsan alleviated influenza-induced acute lung injury by regulating Lactobacillus murinus.

ETHNOPHARMACOLOGICAL RELEVANCE: Sheng Jiangsan (SJS) authorized by the Chinese Food and Drug Administration for treating wind-heat common cold, exhibits broad-spectrum antiviral activity. However, its specific antiviral and anti-inflammatory mechanisms require clarification. Gut microbiota and their metabolites play significant roles in lung disease progression and intervention, yet no research has explored whether the anti-influenza effect of SJS-derived Qingjie-Tuire (QT) Granule involves these pathways.

AIM OF THE STUDY: This study aimed to determine whether QT Granule exerts its anti-influenza effects through modulation of gut microbiota and metabolites, specifically investigating associated antiviral and anti-inflammatory mechanisms. An experimental study employing influenza-infected mice. Mechanistic analysis integrated 16S rRNA full-length sequencing, UHPLC-MS/MS metabolomics, fecal microbiota transplantation (FMT), and targeted probiotic intervention.

MATERIALS AND

METHODS

Influenza-infected mice received QT Granule treatment. Gut microbiota composition was analyzed via full-length 16S rRNA sequencing. Metabolite profiles were assessed using UHPLC-MS/MS. Functional validation involved QT-treated mice FMT into infected mice and supplementing infected mice with Lactobacillus murinus and Lactobacillus reuteri (species enriched by QT). Outcomes included lung pathology, viral titers, survival, and lung/intestinal inflammation, and intestinal barrier integrity.

RESULTS

QT treatment significantly reduced lung pathological damage, lowered viral titers, restored pulmonary macrophage and T-cell proportions, decreased p-STAT1/p-STAT3/p-ERK expression, maintained intestinal barrier function, attenuated lung and intestinal inflammation, and prolonged survival time/survival rate in infected mice. QT intervention restored influenza-depleted UFAs, including docosahexaenoic acid (DHA) and arachidonic acid (AA), and enriched L. murinus and L. reuteri. Crucially, both FMT using QT-treated mouse feces and direct supplementation with L.murinus/L. reuteri replicated QT's core therapeutic effects.

CONCLUSIONS

QT Granule exerts potent anti-influenza and anti-inflammatory effects by modulating gut microbiota (specifically enriching L.murinus and L.reuteri) and restoring UFA metabolites. This gut-lung axis mechanism provides novel insight into traditional Chinese medicine intervention in viral lung diseases.