Microbiome disturbance and resilience dynamics of the upper respiratory tract during influenza A virus infection

Drishti Kaul,Ignacio Mena,Indresh Singh,Karen E Nelson,Rafael A Medina,Barbara A Methe,Raveen Rathnasinghe,Isolda Budnik,Mirco Schmolke,Chris L Dupont,Marcela Ferres,Brett E Pickett,Adolfo García-Sastre,Suman R Das,Gene S Tan,Aldo Barrera,David Wentworth,Rebecca A Halpin,Randy A Albrecht

doi:10.1038/s41467-020-16429-9

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.

Highlights

Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation
The dynamics and relative abundances of bacteria in the upper respiratory tract (URT) microbiome were examined by pyrosequencing of the V1–V3 region of the 16S rRNA, which yielded a total of 2.3 million sequences, which clustered into 707 operational taxonomic units (OTUs) (Table 1)
The microbiome for the Influenza A virus (IAV)-infected cohort is more dynamic than that of the uninfected IAV-free cohort, validating the Anna Karenina principle of microbiomes[21], which refers to the notion that there is much more variability in the microbial communities of infected individuals than in healthy individuals

Summary

Introduction

Infection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation. Influenza A virus (IAV) is a highly infectious upper respiratory tract (URT) disease in humans and animals caused by a negative-sense segmented RNA virus It is recognized as a major public health concern resulting yearly in significant disease and economic burden. Frequent nucleotide substitutions lead to changes on the hemagglutinin and neuraminidase glycoproteins on the surface of IAV particles ( known as antigenic drift) that contribute to the need for continuous vaccine updates This evolutionary arms race between vaccine design and viral mutation contributes to annual influenza epidemics worldwide, which on average results in 3–5 million cases of severe illness and up to 291,000 to 646,000 deaths annually[1]. Humans and ferrets share similar lung physiology, and both are known to be susceptible and transmit the same strains of the IAVs19,20 This has made the ferrets an ideal model to study the dynamics of IAV infection in URT. Our results suggest that microbiome disturbance and resilience dynamics may be critical to addressing the bacterial co-infections associated with influenza-derived morbidity

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Results