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Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1\u20133 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNF\u03b1 and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators.<\/jats:p>","DOI":"10.3390\/ijms231810643","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T21:06:52Z","timestamp":1663103212000},"page":"10643","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Replication of Human Norovirus in Mice after Antibiotic-Mediated Intestinal Bacteria Depletion"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1698-5062","authenticated-orcid":false,"given":"Cristina","family":"Santiso-Bell\u00f3n","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Medicine, University of Valencia, Av. 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Blasco Ib\u00e1\u00f1ez 17, 46010 Valencia, Spain"},{"name":"Instituto de Investigaci\u00f3n INCLIVA, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Rubio-del-Campo","sequence":"additional","affiliation":[{"name":"Department of Food Biotechnology, Instituto de Agroqu\u00edmica y Tecnolog\u00eda de Alimentos (IATA-CSIC), Av. Agust\u00edn Escardino 7, 46980 Paterna, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazaret","family":"Pe\u00f1a-Gil","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine, University of Valencia, Av. 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