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 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.

Exploring Changes in the Host Gut Microbiota During a Controlled Human Infection Model for Campylobacter jejuni

“…In this way, our CHIM offers the ability to study three potential dysbiosis-inciting events: antibiotic prophylaxis with rifaximin, challenge with C. jejuni , and administration of dual antibiotic treatment with ciprofloxacin and azithromycin. Previous CHIM studies focusing on enterotoxigenic Escherichia coli (ETEC) and norovirus and the human gut using either 16S rRNA gene sequencing or metagenomics exist; however, none have specifically targeted the changes in the human gut microbiome during C. jejuni infection ( Pop et al., 2016 ; Patin et al., 2020 ).…”

Partners in Infectious Disease: When Microbes Facilitate Enteric Viral Infections

“…In another study, Chen et al observed increased Proteobacteria in HuNoV infected children compared with healthy controls [24]. Microbiome analysis of symptomatic and asymptomatic HuNoV-infected patients by 16S rRNA sequencing revealed enrichment in Clostridia (Firmicutes) and depletion of Bacteroidia (Bacteroidetes) in symptomatic individuals compared with asymptomatic individuals [51]. These studies point to alterations in the gut microbiota in response to HuNoV.…”

The Interplay between the Host Microbiome and Pathogenic Viral Infections

“…Pigs with highly diverse microbiomes or hosting nonpathogenic E. coli strains have an improved outcome after being infected with the porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) ( 51 ). Patin et al ( 52 ) studied the microbiomes of humans and then challenged them with norovirus. They compared the prechallenge microbiome of people with symptoms of virus infection against that of people without symptoms.…”