Ethnopharmacological relevance: Dysregulation of the upper respiratory tract microbiota, host metabolite profiles, and immune lymphocyte subpopulations is critical in the pathogenesis of respiratory tract infectious diseases (RTIs). Sang Zhu Yang Zheng herbal tea (SZYZ) has emerged as a promising intervention for RTIs, yet its underlying mechanism remains unclear.
Aim of the study: This study aims to investigate the immunomodulatory mechanisms of SZYZ underlying its role in the prevention and treatment of RTIs.
Materials and methods: Human studies were conducted to investigate SZYZ's immunomodulatory effects in preventing RTIs in healthy individuals. In healthy human subjects, SZYZ administration was evaluated for its impact on immune cell counts, airway microbiota composition, and metabolic profiles using advanced sequencing and metabonomic techniques. Murine models were utilized to explore SZYZ's preventive and therapeutic effects, as well as its underlying mechanisms against RTIs, with a focus on influenza A virus (IAV) infection. Murine models were employed with H1N1 PR8 virus infection, and study the therapeutic efficacy and mechanisms of SZYZ alone or in combination with oseltamivir.
Results: In healthy humans, SZYZ profoundly increased the total T cells, B cells, CD4+ T cells, and CD8+ T cells. 16S rRNA sequencing showed decreased airway microbes' diversity, enrichment of the genera Bacteroides and Bifidobacterium, and lowered phyla Actinobacteria, Synergistetes, and several opportunistic pathogens, including Actinomyces, Fretibacterium, Mobiluncus, and Cloacibacillus, and inhibited microbe functions of human disease and bacterial infectious pathways, after administration. Serum and fecal metabonomic identified changes in 138 and 197 metabolites, respectively. Airway Actinobacteria were negatively corelated to total T cells and CD8+T cells count. Serum methyl hexadecanoic acid levels were negatively correlated with T cell counts and positively with Actinobacteria abundance. In IAV-infected mice, SZYZ, administered either as a prophylactic intervention or in combination with oseltamivir, significantly reduced mortality and pathological damage, which were related to immunomodulatory mechanisms of oxidative stress, inflammatory cytokines, and lymphocyte ratio.
Conclusion: We comprehensively elucidate the immunomodulatory effects of SZYZ's on microbiota, metabolism, and lymphocyte subpopulations, which provides a new therapeutic approach for the prevention and treatment of RTIs.
Keywords: Chinese herbal tea; Lymphocyte subpopulations; Metabonomics; Microbiome; Respiratory tract infections; Traditional Chinese medicine.
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