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

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Rodrigues, Patricia Brito ; Gomes, Giovanni Freitas ; Angelim, Monara K. S. C. ; Souza, Gabriela F. ; Muraro, Stefanie Primon ; Toledo-Teixeira, Daniel A. ; Cruz Rattis, Bruna Amanda ; Passos, Amanda Stephane ; Pral, Lais Passarielo ; Rodovalho, Vinicius de Rezende ; Gomes, Arilson Bernardo dos Santos P. ; Matheus, Valquiria Aparecida ; Leao Marcelo Antunes, Andre Saraiva ; Crunfli, Fernanda ; Antunes, Krist Helen ; Duarte de Souza, Ana Paula ; Consonni, Silvio Roberto ; Leiria, Luiz Osorio ; Alves-Filho, Jose Carlos ; Cunha, Thiago M. ; Moraes-Vieira, Pedro M. M. ; Luiz Proenca-Modena, Jose ; Vinolo, Marco Aurelio R.

• Document type: Journal article
• Source: CELLS; v. 11, n. 16, p. 16-pg., 2022-08-01.

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. (AU)

• FAPESP's process: 20/10282-7 - Exploring the molecular basis of SARS-CoV-2 infection in preclinical neural models
• Grantee: Andre Saraiva Leao Marcelo Antunes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/04558-0 - Characterization of intrinsic risk factors and the development of new diagnostic and treatment alternatives for COVID-19
• Grantee: José Luiz Proença Módena
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/05211-3 - Evaluation of Amphiregulin as a prognostic biomarker of severity and its participation in the pathophysiology of COVID-19
• Grantee: José Carlos Farias Alves Filho
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/06372-3 - Multiparametric flow cytometry
• Grantee: Alessandro dos Santos Farias
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 20/04583-4 - Impact of intestinal microbiota and its metabolites on SARS-CoV-2 infection
• Grantee: Marco Aurélio Ramirez Vinolo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/04746-0 - Understanding the molecular bases and the role of risk factors associated to SARS-CoV-2 infection in preclinical models
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Regular Research Grants