Effects of Modified Xuanbai Chengqi Decoction against secondary Streptococcus pneumoniae infection following influenza virus infection: A multi-omics analysis.

Ethnopharmacological Relevance: The Modified Xuanbai Chengqi Decoction (XBCQ), derived from the classical formula "Xuanbai Chengqi Decoction," is a traditional Chinese herbal preparation. Traditional Chinese Medicine (TCM) is crucial for influenza management. Our previous studies have demonstrated the therapeutic effects of XBCQ on pulmonary and intestinal injuries induced by influenza A virus (IAV)/Streptococcus pneumoniae (SPN) co-infection, although the underlying gut-lung axis mechanisms remain to be further elucidated.

Aim Of The Study: We hypothesize that XBCQ ameliorates secondary SPN infection by modulating the gut-lung axis through microbiota-metabolite-immune interactions, and we will evaluate its protective effects and mechanistic basis against IAV-induced secondary SPN infection through integrated multi-omics analyses (gut microbiota and metabolomics).

Materials And Methods: Chemical profiling of XBCQ was performed using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). A sequential infection model was established by intranasal inoculation of IAV followed by SPN to mimic post-influenza secondary bacterial infection. Therapeutic efficacy was validated through quantification of viral/bacterial loads, histopathological analysis, inflammatory cytokines, and intestinal tight junction (TJ) proteins, demonstrating XBCQ's protective effects on both pulmonary and colonic tissues. 16s RNA sequencing and metabonomics were used to evaluate the mechanism of XBCQ intervention in secondary bacterial infection after influenza.

Results: UHPLC-Q-Orbitrap-HRMS analysis identified 60 bioactive components in XBCQ, including sucrose, adenosine, guanosine, and mulberroside A. XBCQ reduced SPN burden by 81.9 %, restored gut microbiota balance, and modulated host metabolic profiles. Correlation analysis revealed that the microbiota altered by XBCQ was significantly associated with pharmacodynamic indicators and metabolites, further confirming the reliability of these findings.

Conclusions: XBCQ prevents SPN superinfection following IAV infection by modulating the microbiota-gut-lung axis. These findings provide a potential scientific basis for the clinical application of XBCQ, offering prospective guidance for preventing bacterial pneumonia during influenza seasons.