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Baicalin (7‐d‐glucuronic acid‐5, 6‐dihydroxyflavone) derived from the root of Scutellaria baicalensis used as Traditional Chinese Medicine (TCM) has been revealed to exert potential antiviral activity via various pathways, while the molecular mechanisms have not been fully understood. Pyroptosis, an inflammatory form of programmed cell death (PCD), is reported to play a crucial role in host cell fate during viral infection. In this study, transcriptome analysis of mice lung tissue reveals that baicalin reverses the alterations of the mRNA levels of PCD‐associated genes upon H1N1 challenge, with a concomitant decrease in the population of H1N1‐induced propidium iodide (PI)+ and Annexin Ⅴ+ cells. Intriguingly, we find that baicalin contributes to the survival of infected lung alveolar epithelial cells partly through its inhibition of H1N1‐induced cell pyroptosis, which is manifested by reduced bubble‐like protrusion cells and lactate dehydrogenase (LDH) release. Moreover, the antipyroptosis effect of baicalin in response to H1N1 infection is found to be mediated by its repression on caspase‐3/Gasdermin E (GSDME) pathway. Cleaved caspase‐3 and N‐terminal fragment of GSDME (GSDME‐N) are detected in H1N1‐infected cell lines and mice lung tissues, which are markedly reversed by baicalin treatment. Furthermore, inhibition of caspase‐3/GSDME pathway by caspase‐3 inhibitor or siRNA exerts an antipyroptosis effect equal to that of baicalin treatment in infected A549 and BEAS‐2B cells, indicating a pivotal role of caspase‐3 in the antiviral activities of baicalin. Conclusively, for the first time, we demonstrate that baicalin could effectively suppress H1N1‐induced pyroptosis of lung alveolar epithelial cells via caspase‐3/GSDME pathway both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

The oral and upper respiratory tracts are closely linked anatomically and physiologically with the lower respiratory tract and lungs, and the influence of oral and upper respiratory microbes on the lung microbiota is increasingly being recognized. However, the ecological process and individual heterogeneity of the oral and upper respiratory tract microbes shaping the lung microbiota remain unclear owing to the lack of controlled analyses with sufficient sample sizes. Here, the microbiomes of saliva, nasal cavity, oropharyngeal area, and bronchoalveolar lavage samples are profiled and the shaping process of multisource microbes on the lung microbiota is measured. It is found that oral and nasal microbial inputs jointly shape the lung microbiota by occupying different ecological niches. It is also observed that the spread of oral microbes to the lungs is heterogeneous, with more oral microbes entering the lungs being associated with decreased lung function and increased lung proinflammatory cytokines. These results depict the external shaping process of lung microbiota and indicate the great value of oral samples, such as saliva, in monitoring and assessing lung microbiota status in clinical settings. [ABSTRACT FROM AUTHOR]