Abstract
Background
The respiratory tract houses a specialized microbial ecosystem, and despite the close anatomical and physiological ties between the oral, upper respiratory, and lower respiratory tracts, there is a substantial discrepancy in microbial quantity, spanning multiple orders of magnitude. The potential for commensal bacteria to prevent infection lies in their ability to regulate innate and adaptive host immune responses. Influenza virus predominantly targets and replicates within the epithelial cells of both upper and lower respiratory tracts. Given this, we hypothesize that the nasal-lung-microbe cross-talk plays a crucial role in influencing influenza susceptibility. In this study, we investigated viral presence, gene expression profiles of host, and the nasal and lung microbiota in a beagle dog model with antibiotic-induced nasal dysbiosis during influenza virus infection.
Results
In this study, using 16S rRNA sequencing, combined with comparative anatomy, transcriptomics and histological examination, we investigated viral presence, gene expression profiles of host, and the nasal and lung microbiota in influenza-infected beagles with antibiotic-induced nasal dysbiosis. Our data showed that dysbiosis of the nasal microbiome exacerbates influenza-induced respiratory disease and the epithelial barrier disruption, and impairs host antiviral responses in the nasal cavity and lung. Moreover, dysregulation of nasal microbiota worsens the influenza-induced disturbance in lung microbiota. Further, we identified one strain of Lactobacillus plantarum with a significant antiviral effect, which is exerted by activating the IFN pathway and modulating the impaired autophagy flux induced by influenza virus. Our data collectively indicate a close connection between the microbiomes of different ecological niches in the nasal and lung regions. This connection significantly influences subsequent host-microbe cross-talk, which was associated with an increased susceptibility to influenza.
Conclusions
Our investigation reveals that nasal microbiota dysbiosis not only increases host susceptibility to influenza virus infection but also contributes to the exacerbation of influenza-induced lung microbiota dysregulation. This intricate relationship extends to the microbiome composition, demonstrating correlations with critical factors such as host antiviral responses, inflammation thresholds, and mucosal barrier integrity. Together, these findings underscore the substantial impact of nasal microbiota dysbiosis on the overall outcome during influenza infections.