Respiratory Disease following Viral Lung Infection Alters the Murine Gut Microbiota.

Helen T Groves,Michael J Cox,Miriam F Moffatt,Leah Cuthbertson,Phillip James,John S Tregoning

doi:10.3389/fimmu.2018.00182

Abstract

Alterations in the composition of the gut microbiota have profound effects on human health. Consequently, there is great interest in identifying, characterizing, and understanding factors that initiate these changes. Despite their high prevalence, studies have only recently begun to investigate how viral lung infections have an impact on the gut microbiota. There is also considerable interest in whether the gut microbiota could be manipulated during vaccination to improve efficacy. In this highly controlled study, we aimed to establish the effect of viral lung infection on gut microbiota composition and the gut environment using mouse models of common respiratory pathogens respiratory syncytial virus (RSV) and influenza virus. This was then compared to the effect of live attenuated influenza virus (LAIV) vaccination. Both RSV and influenza virus infection resulted in significantly altered gut microbiota diversity, with an increase in Bacteroidetes and a concomitant decrease in Firmicutes phyla abundance. Although the increase in the Bacteroidetes phylum was consistent across several experiments, differences were observed at the family and operational taxonomic unit level. This suggests a change in gut conditions after viral lung infection that favors Bacteroidetes outgrowth but not individual families. No change in gut microbiota composition was observed after LAIV vaccination, suggesting that the driver of gut microbiota change is specific to live viral infection. Viral lung infections also resulted in an increase in fecal lipocalin-2, suggesting low-grade gut inflammation, and colonic Muc5ac levels. Owing to the important role that mucus plays in the gut environment, this may explain the changes in microbiota composition observed. This study demonstrates that the gut microbiota and the gut environment are altered following viral lung infections and that these changes are not observed during vaccination. Whether increased mucin levels and gut inflammation drive, or are a result of, these changes is still to be determined.

Highlights

The bacteria that colonize the gastrointestinal tract, known collectively as the gut microbiota, play many roles in maintaining human health, such as promoting the development of the mucosa and aiding nutrient metabolism
We demonstrate that the composition of the gut microbiota changes after viral lung infection
The constituent bacteria that drove these changes varied at the family and Operational taxonomic units (OTUs) levels, suggesting that viral lung infection creates conditions favorable to support a Bacteroidetes bloom, but that the species that make up this bloom are selected by currently unknown factors

Summary

Introduction

The bacteria that colonize the gastrointestinal tract, known collectively as the gut microbiota, play many roles in maintaining human health, such as promoting the development of the mucosa and aiding nutrient metabolism. The gut microbiota has systemic influences outside the gastrointestinal tract, from the wide-ranging anti-inflammatory effects of bacterial metabolites like short-chain fatty acids to the alteration of neurotransmitter production in the central nervous system [2, 3]. Given its impact on health, research has focused on understanding what factors influence the composition of the gut microbiota. Infection shapes the gut microbiota, but the majority of research has focused on gastrointestinal infections or infections that have an impact on the immune response, such as HIV [10, 11]. Despite their very high prevalence, little is known about how lung infections affect the gut microbiota

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