Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity

Abstract

Background: 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. 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. Results: We enrolled 95 infants from Le Bonheur during the 2014 to 2016 RSV season. Of these, 37 were wellbabies 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). Conclusions: Collectively, 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.

Comparative Fecal Microbiota Analysis of Infants With Acute Bronchiolitis Caused or Not Caused by Respiratory Syncytial Virus

“…Consistently, this likeness reinforces the finding of certain bacterial genera (e.g., Bacteroides ) potentially affecting the bronchiolitis course in our infants. The present study’s results are also reminiscent of those from a very recent investigation that showed an altered gut microbiota to be associated with RSV disease severity ( Harding et al., 2020 ). However, restricting our study to a single sample from each enrolled infant hindered us from providing any statistical inference or causality of the fecal bacterial composition with the illness severity as well as from investigating the differences in bacterial composition at the species level or in bacterial functionality between bronchiolitis infants’ groups.…”

Mechanisms linking the human gut microbiome to prophylactic and treatment strategies for COVID-19

“…Research into respiratory syncytial virus of infants, a key cause of LRTI, has shown an altered microbial community to be associated with severe disease symptoms (84) . A recent review by Enaud et al (85) documented current knowledge about the gut-lung axis.…”

Early-Life Lung and Gut Microbiota Development and Respiratory Syncytial Virus Infection

“…Harding et al. investigated stool samples collected by 95 babies, 37 healthy and 53 RSV-positive infants hospitalized (moderate RSV-disease) and 5 RSV-positive infants transferred to the pediatrician intensive care unit (ICU) (Severe RSV-disease) ( 89 ). All stool samples were collected within 72 hours of admission to analyze gut microbiota.…”

“…In the infants with severe RSV-disease group, the authors observed slightly lower alpha diversity, representing the richness and evenness of the bacterial community compared with moderate RSV-disease and healthy controls. While this study has limitations since it cannot determine if the changes are the cause or the consequence of the infection, the timing of the sample collection (72 hours post-hospitalization) could indicate that early-life gut microbiome composition correlates with RSV-disease severity ( 89 ). Considering the hypothesis of the gut-lung axis, it is reasonable that gut dysbiosis affects disease severity in patients with RSV infection.…”