Microbiota Depletion Promotes Human Rotavirus Replication in an Adult Mouse Model.

Roberto Gozalbo-Rovira,Antonio Rubio-Del-Campo,Javier Buesa,Jesús Rodríguez-Díaz,Susana Vila-Vicent,Cristina Santiso-Bellón,Vicente Monedero,María J Yebra,Carlos Muñoz

doi:10.3390/biomedicines9070846

Abstract

Intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of analyzing whether human gut bacteria improve the inefficient replication of human rotavirus in mice, we performed fecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. We showed that a simple antibiotic treatment, irrespective of FMT, resulted in viral shedding for 6 days after challenge with the human rotavirus G1P[8] genotype Wa strain (RVwa). Rotavirus titers in feces were also significantly higher in antibiotic-treated animals with or without FMT but they were decreased in animals subject to self-FMT, where a partial re-establishment of specific bacterial taxons was evidenced. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members of Lactobacillus, Bilophila, Mucispirillum, and Oscillospira, recovered after self-FMT. In antibiotic-treated and FMT animals where the virus replicated more efficiently, differences were observed in gene expression of immune mediators, such as IL1β and CXCL15, as well as in the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human rotavirus infectivity in mice.

Highlights

We showed that a simple microbial ablation through antibiotics was sufficient to promote human RV infection in mice, highlighting a role for intestinal microbiota in suppressing these RVs in the murine model
In the mouse model could be improved by replacing its intestinal microbiota with the microbiota of infants by fecal microbiota transplant (FMT) using antibiotic (Ab)-mediated microbiota ablation
Given the lack of an efficient mouse model to replicate relevant human RV strains [13], we studied whether mice could be infected with rotavirus G1P[8] genotype Wa strain (RVwa) after an infant gut microbiota engraftment

Summary

Introduction

Diarrheal disease is the second leading cause of death worldwide in children under five years of age, accounting for around 525,000 deaths each year. Rotavirus (RV) is among the predominant causes of non-bacterial acute gastroenteritis in infant and young children, with an estimated 150,000 deaths per year, mostly in developing countries [1]. The gut is a very complex ecosystem, with multiple interactions between the host immune system, glycobiology, resident microbiota, and viruses responsible for gastroenteritis [2,3,4,5]. A link between human RV infection and intestinal bacterial populations has been revealed from analysis of the microbiota in population groups displaying different vaccine take after inoculation with RV live vaccines [6,7]. Some microorganisms, including probiotic bacteria, directly interact with RV and potentially block their binding to epithelial receptors, counteracting infection [9]

Methods

Results

Conclusion