Altered Gut Microbiota in Infants is Associated with Respiratory Syncytial Virus Disease Severity

Abstract

Rationale Respiratory 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.Objectives Our objective was to determine the gut microbial profile associated with severe RSV patients, which could be used to help identify future at-risk patients and develop therapeutically protective microbial assemblages that may stimulate immuno-protection.Methods We enrolled 58 infants hospitalized with RSV, 5 were admitted to the pediatric intensive care unit and thus considered severe, 53 were admitted to the pediatric ward and considered moderate, and 37 healthy controls collected from infants during “well-baby checkups” from 2012 to 2015. We evaluated the composition of gut microbiota within 72 hours of enrollment in these patients via 16s sequencing of fecal DNA.Measurements and Main Results There was a significant enrichment in S24_7, Clostridiales, Odoribacteraceae, Lactobacillaceae, and Actinomyces in RSV 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 (severe and moderate) compared to controls and had significant microbial composition separating all three groups (control, moderate RSV, and Severe RSV). Conclusions Collectively, these data indicate that a unique gut microbial profile that is associated with severe RSV disease. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of severe RSV disease.