The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study

ABSTRACT Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbio...

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Autores principales: N. V. Patin, A. Peña-Gonzalez, J. K. Hatt, C. Moe, A. Kirby, K. T. Konstantinidis
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Publicado: American Society for Microbiology 2020
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spelling oai:doaj.org-article:46993a4441014934bb15cf4b8a88e4642021-11-15T15:55:43ZThe Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study10.1128/mBio.02634-202150-7511https://doaj.org/article/46993a4441014934bb15cf4b8a88e4642020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02634-20https://doaj.org/toc/2150-7511ABSTRACT Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbiome response to norovirus infection, which has important implications for diagnostics and host recovery. Here, we characterized the gut microbiomes of subjects enrolled in a norovirus challenge study. We analyzed microbiome features of asymptomatic and symptomatic individuals at the genome (population) and gene levels and assessed their response over time in symptomatic individuals. We show that the preinfection microbiomes of subjects with asymptomatic infections were enriched in Bacteroidetes and depleted in Clostridia relative to the microbiomes of symptomatic subjects. These compositional differences were accompanied by differences in genes involved in the metabolism of glycans and sphingolipids that may aid in host resilience to infection. We further show that microbiomes shifted in composition following infection and that recovery times were variable among human hosts. In particular, Firmicutes increased immediately following the challenge, while Bacteroidetes and Proteobacteria decreased over the same time. Genes enriched in the microbiomes of symptomatic subjects, including the adenylyltransferase glgC, were linked to glycan metabolism and cell-cell signaling, suggesting as-yet unknown roles for these processes in determining infection outcome. These results provide important context for understanding the gut microbiome role in host susceptibility to symptomatic norovirus infection and long-term health outcomes. IMPORTANCE The role of the human gut microbiome in determining whether an individual infected with norovirus will be symptomatic is poorly understood. This study provides important data on microbes that distinguish asymptomatic from symptomatic microbiomes and links these features to infection responses in a human challenge study. The results have implications for understanding resistance to and treatment of norovirus infections.N. V. PatinA. Peña-GonzalezJ. K. HattC. MoeA. KirbyK. T. KonstantinidisAmerican Society for Microbiologyarticlehuman microbiomemetagenomicsnorovirusesMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution DOAJ
collection DOAJ
language EN
topic human microbiome
metagenomics
noroviruses
Microbiology
QR1-502
spellingShingle human microbiome
metagenomics
noroviruses
Microbiology
QR1-502
N. V. Patin
A. Peña-Gonzalez
J. K. Hatt
C. Moe
A. Kirby
K. T. Konstantinidis
The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study
description ABSTRACT Norovirus infections take a heavy toll on worldwide public health. While progress has been made toward understanding host responses to infection, the role of the gut microbiome in determining infection outcome is unknown. Moreover, data are lacking on the nature and duration of the microbiome response to norovirus infection, which has important implications for diagnostics and host recovery. Here, we characterized the gut microbiomes of subjects enrolled in a norovirus challenge study. We analyzed microbiome features of asymptomatic and symptomatic individuals at the genome (population) and gene levels and assessed their response over time in symptomatic individuals. We show that the preinfection microbiomes of subjects with asymptomatic infections were enriched in Bacteroidetes and depleted in Clostridia relative to the microbiomes of symptomatic subjects. These compositional differences were accompanied by differences in genes involved in the metabolism of glycans and sphingolipids that may aid in host resilience to infection. We further show that microbiomes shifted in composition following infection and that recovery times were variable among human hosts. In particular, Firmicutes increased immediately following the challenge, while Bacteroidetes and Proteobacteria decreased over the same time. Genes enriched in the microbiomes of symptomatic subjects, including the adenylyltransferase glgC, were linked to glycan metabolism and cell-cell signaling, suggesting as-yet unknown roles for these processes in determining infection outcome. These results provide important context for understanding the gut microbiome role in host susceptibility to symptomatic norovirus infection and long-term health outcomes. IMPORTANCE The role of the human gut microbiome in determining whether an individual infected with norovirus will be symptomatic is poorly understood. This study provides important data on microbes that distinguish asymptomatic from symptomatic microbiomes and links these features to infection responses in a human challenge study. The results have implications for understanding resistance to and treatment of norovirus infections.
format article
author N. V. Patin
A. Peña-Gonzalez
J. K. Hatt
C. Moe
A. Kirby
K. T. Konstantinidis
author_facet N. V. Patin
A. Peña-Gonzalez
J. K. Hatt
C. Moe
A. Kirby
K. T. Konstantinidis
author_sort N. V. Patin
title The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study
title_short The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study
title_full The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study
title_fullStr The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study
title_full_unstemmed The Role of the Gut Microbiome in Resisting Norovirus Infection as Revealed by a Human Challenge Study
title_sort role of the gut microbiome in resisting norovirus infection as revealed by a human challenge study
publisher American Society for Microbiology
publishDate 2020
url https://doaj.org/article/46993a4441014934bb15cf4b8a88e464
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