Nasal microbiota clusters associate with inflammatory response, viral load, and symptom severity in experimental rhinovirus challenge

Markus J Lehtinen,Liisa Lehtoranta,Ronald B Turner,Tommi Kauko,Anna Lyra,Ashley A Hibberd,Sampo J Lahtinen,Sofia Forssten,Nicolas Yeung,Sofia Männikkö,Buffy Stahl

doi:10.1038/s41598-018-29793-w

Markus J Lehtinen, Liisa Lehtoranta + Show 9 more

Open Access

https://doi.org/10.1038/s41598-018-29793-w

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Abstract

The role of nasal and fecal microbiota in viral respiratory infections has not been established. We collected nasal swabs and washes, and fecal samples in a clinical study assessing the effect of probiotic Bifidobacterium animalis subsp. lactis Bl-04 on experimental rhinovirus infection. The nasal and fecal microbiota were characterized by 16S rRNA gene sequencing. The resulting data were compared with nasal inflammatory marker concentrations, viral load, and clinical symptoms. By using unsupervised clustering, the nasal microbiota divided into six clusters. The clusters predominant of Staphylococcus, Corynebacterium/Alloiococcus, Moraxella, and Pseudomonadaceae/Mixed had characteristic inflammatory marker and viral load profiles in nasal washes. The nasal microbiota clusters of subjects before the infection associated with the severity of clinical cold symptoms during rhinovirus infection. Rhinovirus infection and probiotic intervention did not significantly alter the composition of nasal or fecal microbiota. Our results suggest that nasal microbiota may influence the virus load, host innate immune response, and clinical symptoms during rhinovirus infection, however, further studies are needed.

Highlights

Rhinoviruses are an important cause of respiratory illness
We investigated whether the clusters associate with changes in nasal wash inflammatory marker concentrations and viral load at D0–D5 by examining subjects based on their D0 cluster
The microbiota clusters appear to associate with different inflammatory response, viral titer, and symptom severity profiles in rhinovirus infection

Summary

Introduction

Rhinoviruses are an important cause of respiratory illness. Adults have 1–2 rhinovirus infections each year and approximately 60% of these infections are associated with symptoms[1,2]. The concentration of pro-inflammatory cytokines in nasal lavage has a modest correlation with symptom severity, and expression of innate immunity-associated genes reliably distinguishes symptomatic from asymptomatic infections[4,5,6]. These observations suggest that modulation of the innate host response is a potential target for intervention in these illnesses. Nasal swabs and fecal samples collected during the latter study were used to explore the interactions among the nasal and fecal host microbiota, the administration of probiotic, and the clinical results of the viral infection under controlled conditions

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