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. 2020 May 21;11(1):2537.
doi: 10.1038/s41467-020-16429-9.

Microbiome Disturbance and Resilience Dynamics of the Upper Respiratory Tract During Influenza A Virus Infection

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Free PMC article

Microbiome Disturbance and Resilience Dynamics of the Upper Respiratory Tract During Influenza A Virus Infection

Drishti Kaul et al. Nat Commun. .
Free PMC article

Abstract

Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation. The effects of influenza infection on the upper respiratory tract (URT) microbiome are largely unknown. Here, we report a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes have stable healthy ecostate communities both within and between individuals. In contrast, infected patients and ferrets exhibit large changes in bacterial community composition over time and between individuals. The unhealthy ecostates of infected individuals progress towards the healthy ecostate, coinciding with viral clearance and recovery. Pseudomonadales associate statistically with the disturbed microbiomes of infected individuals. The dynamic and resilient microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Diversity of the URT microbiome of human patients infected with influenza A virus (IAV).
Beta-diversity analysis for longitudinal nasopharyngeal swab samples obtained from healthy and IAV-infected individuals. Principal coordinates analysis (PCoA) of Bray–Curtis distances was done for samples from humans, labeled as influenza positive in red (P, indicating data points with positive IAV qRT-PCR detection), influenza unknown in yellow (U, indicates time points from positive individuals that were below the qRT-PCR detection limits at different time points after the onset of symptoms), and uninfected samples in blue (Flu negative). The total variability explained by all three principal coordinates (PCs) is shown on the axes. Source data are provided as a Source Data file.
Fig. 2
Fig. 2. Comprehensive taxonomic breakdown for IAV-free (left) and IAV-infected (right) human subjects.
a Each column is a specific sample. The plot summarizes the relative taxonomic abundances at the class level for taxonomic groups that are present in >5% of the samples (see legend below), sorted in decreasing order by the most abundant taxonomic group in each cohort. Gammaproteobacteria (Pseudomonas, orange) bloom is prevalent among the infected patients (right), whereas Actinobacteria is the most abundant among healthy patients. b An order (left) and family (right) level breakdown of the Gammaproteobacteria observed in infected patients. Source data are provided as a Source Data file.
Fig. 3
Fig. 3. Diversity of the URT microbiome in ferrets during IAV infection.
Beta-diversity analysis for longitudinal URT samples taken after experimental infection with the A/Netherlands/602/09 H1N1 strain (Infected) or in control animals. Principal coordinates analysis (PCoA) of Bray–Curtis distances was performed for all samples. Data points for uninfected ferrets are in blue, the T = 0 for the infected ferrets in lavender, the T = 14 for infected ferrets in cyan, and all other infected time points were collected at 1–7 days post infection and shown are in red. The total variability explained by all three principal coordinates (PCs) is shown on the axes. Each group of ferret was composed of seven animals. Source data are provided as a Source Data file.
Fig. 4
Fig. 4. Qualitative and quantitative representation of the temporal trajectory of the ferret microbiome.
a Percent body weights of groups of seven ferrets mock inoculated (uninfected) or intranasally infected with 1 × 106 pfu of influenza A/Neth/602/09 virus. Body weights were determined daily for 14 days, and are represented as the average percent body weight compared with the initial weight of each animal on the day of inoculation and error bars are the standard deviation for each time point. b Viral titers of nasal washes of ferrets infected with 1 × 106 pfu of A/Neth/602/09 virus. Nasal washes were obtained on days 1, 3, 5, and 7 post infection, and are represented as the average viral titer of seven infected animals. Error bars indicate the standard deviation for each time point. The limit of detection of the assay was 10 pfu/ml (dashed line). bd Comprehensive taxonomic breakdown of two influenza-infected, both representing divergent baseline microbiomes (c, d) and uninfected ferret (e), at different time points. Taxa abundance values for top ten most prevalent taxa at the order level for different time points (0–14 dpi). Only taxa labels with a confidence score of > = 90% were retained in the analysis. The remaining taxa are pooled into an additional taxon labeled “Other”. f, g The boxplots represent the relative Pseudomonas abundance across all infected (f) and uninfected (g) ferrets (n = 7 for each). The box represents the interquartile range, the horizontal line within the box indicates the median for each sample grouping, observations are indicated by dots, and the whiskers outside the box extend from the highest to the lowest observation represented in the plot. Source data are provided as a Source Data file.

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