Dynamic Changes in the Microbiome and Mucosal Immune Microenvironment of the Lower Respiratory Tract by Influenza Virus Infection

Abstract

Influenza is a major public health concern, and the high mortality rate is largely attributed to secondary bacterial infections. There are several mechanisms through which the virus increases host susceptibility to bacterial colonization, but the micro-environment in lower respiratory tract (LRT) of host, infected with influenza virus, is unclear. To this end, we analyzed the LRT microbiome, transcriptome of lung and metabolome of bronchoalveolar lavage fluid (BALF) in mice inoculated intra-nasally with H1N1 to simulate human influenza, and we observed significant changes in the composition of microbial community and species diversity in the acute (7 days post inoculation or dpi), convalescent (14 dpi) and the recovery (28 dpi) periods. The dominant bacterial class shifted from Alphaproteobacteria to Gammaproteobacteria and Actinobacteria in the infected mice, with a significant increase in the relative abundance of anaerobes and facultative anaerobes like Streptococcus and Staphylococcus. The dysbiosis in the LRT of infected mice was not normalized even in the recovery phase of the infection. In addition, the infected lung transcriptome showed significant differences in the expression levels of genes associated with bacterial infection and immune responses. Finally, the influenza virus infection also resulted in significant changes in the metabolome of the BALF. These alterations in the microbiome, transcriptome, and metabolome of infected lungs were not only appeared at the acute period, but also observed at the recovery period. Furthermore, the infection of influenza virus induced a long-term effect in LRT micro-environmental homeostasis, which may give a chance for the invasion of potential pathogens.

COVID-19 disease: novel clinical manifestations and therapeutic exploration

“…At the same time, the patients' infection parameters needed to be closely monitored. COVID-19, like other viral types of pneumonia, may present as a viral or bacterial infection at an early stage [25][26][27]. A total of five patients with positive pharyngeal swabs for more than 15 days and a decreased lymph count received intravenous immunoglobulin, and their lymphocyte count was reported to have improved significantly.…”

Lung microbiome and coronavirus disease 2019 (COVID-19): Possible link and implications

“…In mice, influenza virus infection of lungs caused a shift in the composition and diversity of microbial community. The viral infection changed the dominant bacterial class from Alphaproteobacteria to Gammaproteobacteria and Actinobacteria , and this was followed by an increase in the relative abundance of Streptococcus and Staphylococcus [44] . In summary, the lung microbiome is highly dynamic, and infections (bacterial, viral) can lead to rapid alterations in the lung microbiome, and the microbial communities can play a critical role in those infections (shown in Fig.…”

New perspectives into the clinical characteristics of COVID-19 disease

“…At the same time, the patient's infection parameters needed to be closely monitored. COVID-19 like other viral types of pneumonia may present as a viral or bacterial infection at an early stage [23][24][25] . A total of 5 patients with positive pharyngeal swabs for morethan15daysandadecreasedlymphcountreceivedintravenous immunoglobulin, and their lymphocyte count was reported to have improved significantly.…”