Scutellaria baicalensis water decoction ameliorates lower respiratory tract infection by modulating respiratory microbiota

Background: The pathogenesis of lower respiratory tract infections (LRTIs) has been demonstrated to be strongly associated with dysbiosis of respiratory microbiota. Scutellaria baicalensis , a traditional Chinese medicine, is widely used to treat respiratory infections. However, whether the therapeutic effect of S. baicalensis on LRTIs depends upon respiratory microbiota regulation is largely unclear. Purpose: To investigate the potential effect and mechanism of S. baicalensis on the respiratory microbiota of LRTI mice. Methods: A mouse model of LRTI was established using Klebsiella pneumoniae or Streptococcus pneumoniae . Antibiotic treatment was administered, and transplantation of respiratory microbiota was performed to deplete the respiratory microbiota of mice and recover the destroyed microbial community, respectively. Highperformance liquid chromatography (HPLC) was used to determine and quantify the chemical components of S. baicalensis water decoction (SBWD). Pathological changes in lung tissues and the expressions of serum inflammatory cytokines, including interleukin-17A (IL -17A), granulocyte -macrophage colony -stimulating factor (GM-CSF), interleukin-6 (IL -6), and tumor necrosis factor- alpha (TNF- alpha), were determined by hematoxylin and eosin (H &E) staining and enzyme -linked immunosorbent assay (ELISA), respectively. Quantitative real-time PCR (qRTPCR) analysis was performed to detect the mRNA expression of GM-CSF. Metagenomic sequencing was performed to evaluate the effect of SBWD on the composition and function of the respiratory microbiota in LRTI mice. Results: Seven main components, including scutellarin, baicalin, oroxylin A-7-O- beta -d-glucuronide, wogonoside, baicalein, wogonin, and oroxylin A, were identified and their levels in SBWD were quantified. SBWD ameliorated pulmonary pathological injury and inflammatory responses in K. pneumoniae and S. pneumoniae -induced LRTI mice, as evidenced by the dose -dependent reductions in the levels of serum inflammatory cytokines, IL -6 and TNF- alpha. SBWD may exert a bidirectional regulatory effect on the host innate immune responses in LRTI mice and regulate the expressions of IL -17A and GM-CSF in a microbiota-dependent manner. K. pneumoniae infection but not S. pneumoniae infection led to dysbiosis in the respiratory microbiota, evident through disturbances in the taxonomic composition characterized by bacterial enrichment, including Proteobacteria, Enterobacteriaceae , and Klebsiella. K. pneumoniae and S. pneumoniae infection altered the bacterial functional profile of the respiratory microbiota, as indicated by increases in lipopolysaccharide biosynthesis, metabolic pathways, and carbohydrate metabolism. SBWD had a certain trend on the regulation of compositional disorders in the respiratory flora and modulated partial microbial functions embracing carbohydrate metabolism in K. pneumoniae -induced LRTI mice. Conclusion: SBWD may exert an anti -infection effect on LRTI by targeting IL -17A and GM-CSF through respiratory microbiota regulation. The mechanism of S. baicalensis action on respiratory microbiota in LRTI treatment merits further investigation.