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

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Cells


. 2022 Aug 18;11(16):2572.
doi: 10.3390/cells11162572.
Impact of Microbiota Depletion by Antibiotics on SARS-CoV-2 Infection of K18-hACE2 Mice


Patrícia Brito Rodrigues ¹ , Giovanni Freitas Gomes ² , Monara K S C Angelim ³ , Gabriela F Souza ⁴ , Stefanie Primon Muraro ⁴ , Daniel A Toledo-Teixeira ⁴ , Bruna Amanda Cruz Rattis ⁵ , Amanda Stephane Passos ^{2 6} , Laís Passarielo Pral ¹ , Vinícius de Rezende Rodovalho ¹ , Arilson Bernardo Dos Santos P Gomes ¹ , Valquíria Aparecida Matheus ¹ , André Saraiva Leão Marcelo Antunes ⁷ , Fernanda Crunfli ⁷ , Krist Helen Antunes ⁸ , Ana Paula Duarte de Souza ⁸ , Sílvio Roberto Consonni ⁹ , Luiz Osório Leiria ^{2 6} , José Carlos Alves-Filho ^{2 6} , Thiago M Cunha ^{2 6} , Pedro M M Moraes-Vieira ^{3 10 11} , José Luiz Proença-Módena ^{4 11} , Marco Aurélio R Vinolo ^{1 10 11}



Affiliations

• PMID: 36010648
• DOI: 10.3390/cells11162572

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.

Keywords: COVID-19; SARS-CoV-2; colon; gut-to-lung axis; intestinal microbiota; respiratory infection.