Abstract

BackgroundRespiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infections in infants. There are still no vaccines or specific antiviral therapies against RSV, mainly due to the inadequate understanding of RSV pathogenesis. Recent data suggest a role for gut microbiota community structure in determining RSV disease severity. Our objective was to determine the gut microbial profile associated with severe RSV patients, which could be used to help identify at-risk patients and develop therapeutically protective microbial assemblages that may stimulate immuno-protection.ResultsWe enrolled 95 infants from Le Bonheur during the 2014 to 2016 RSV season. Of these, 37 were well-babies and 58 were hospitalized with RSV. Of the RSV infected babies, 53 remained in the pediatric ward (moderate) and 5 were moved to the pediatric intensive care unit at a later date (severe). Stool samples were collected within 72 h of admission; and the composition of gut microbiota was evaluated via 16S sequencing of fecal DNA. There was a significant enrichment in S24_7, Clostridiales, Odoribacteraceae, Lactobacillaceae, and Actinomyces in RSV (moderate and severe) vs. controls. Patients with severe RSV disease had slightly lower alpha diversity (richness and evenness of the bacterial community) of the gut microbiota compared to patients with moderate RSV and healthy controls. Beta diversity (overall microbial composition) was significantly different between all RSV patients (moderate and severe) compared to controls and had significant microbial composition separating all three groups (control, moderate RSV, and severe RSV).ConclusionsCollectively, these data demonstrate that a unique gut microbial profile is associated with RSV disease and with severe RSV disease with admission to the pediatric intensive care unit. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of severe RSV disease.

Highlights

  • Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infections in infants

  • Respiratory syncytial virus (RSV) is a ubiquitous respiratory virus infecting the majority of the human population by 1 year of age [1]

  • Because there are a vast number of microbes residing in the gut, there is no shortage of microorganism-associated molecular patterns (MAMPs) as well as pathogen-associated molecular patterns (PAMPs) that can initiate in the gut and alter immune functions in the lung [24]

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Summary

Introduction

Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infections in infants. Our objective was to determine the gut microbial profile associated with severe RSV patients, which could be used to help identify at-risk patients and develop therapeutically protective microbial assemblages that may stimulate immuno-protection. Respiratory syncytial virus (RSV) is a ubiquitous respiratory virus infecting the majority of the human population by 1 year of age [1]. In the U.S alone, RSV causes 85,000 to 144,000 hospitalizations [4], 14,000 deaths [2], and ~ $2.6 billion in medical care costs each year [5]. In view of the fact that RSV is a “significant unmet medical need” [6] with no known vaccine, there is a necessity to find therapeutic approaches to prevent and treat severe RSV infections

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