Impact of Microbiota Depletion by Antibiotics on SARS-CoV-2 Infection of K18-hACE2 Mice

抗生素引起的肠道菌群减少对K18-hACE2小鼠SARS-CoV-2感染的影响

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作者:Patrícia Brito Rodrigues ,Giovanni Freitas Gomes ,Monara K S C Angelim ,Gabriela F Souza ,Stefanie Primon Muraro ,Daniel A Toledo-Teixeira ,Bruna Amanda Cruz Rattis ,Amanda Stephane Passos ,Laís Passarielo Pral ,Vinícius de Rezende Rodovalho ,Arilson Bernardo Dos Santos P Gomes ,Valquíria Aparecida Matheus ,André Saraiva Leão Marcelo Antunes ,Fernanda Crunfli ,Krist Helen Antunes ,Ana Paula Duarte de Souza ,Sílvio Roberto Consonni ,Luiz Osório Leiria ,José Carlos Alves-Filho ,Thiago M Cunha ,Pedro M M Moraes-Vieira ,José Luiz Proença-Módena ,Marco Aurélio R Vinolo

Abstract

Clinical and experimental data indicate that severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection is associated with significant changes in the composition and function of intestinal microbiota. However, the relevance of these effects for SARS-CoV-2 pathophysiology is unknown. In this study, we analyzed the impact of microbiota depletion after antibiotic treatment on the clinical and immunological responses of K18-hACE2 mice to SARS-CoV-2 infection. Mice were treated with a combination of antibiotics (kanamycin, gentamicin, metronidazole, vancomycin, and colistin, Abx) for 3 days, and 24 h later, they were infected with SARS-CoV-2 B lineage. Here, we show that more than 80% of mice succumbed to infection by day 11 post-infection. Treatment with Abx had no impact on mortality. However, Abx-treated mice presented better clinical symptoms, with similar weight loss between infected-treated and non-treated groups. We observed no differences in lung and colon histopathological scores or lung, colon, heart, brain and kidney viral load between groups on day 5 of infection. Despite some minor differences in the expression of antiviral and inflammatory markers in the lungs and colon, no robust change was observed in Abx-treated mice. Together, these findings indicate that microbiota depletion has no impact on SARS-CoV-2 infection in mice.

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