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

Cells. 2022 Aug 18;11(16):2572. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • COVID-19 Drug Treatment*
  • Disease Models, Animal
  • Melphalan
  • Mice
  • Mice, Transgenic
  • Microbiota*
  • Peptidyl-Dipeptidase A / metabolism
  • SARS-CoV-2
  • gamma-Globulins

Substances

  • Anti-Bacterial Agents
  • K-18 conjugate
  • gamma-Globulins
  • Peptidyl-Dipeptidase A
  • Angiotensin-Converting Enzyme 2
  • Melphalan

Grants and funding

This research was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant numbers 2019/19/06372-3, 2020/04583-4, 2020/04746-0, 2020/04558-0, 2020/10282-7 and 2020/05211-3. This study was also funded by Fundo de Apoio ao Ensino, Pesquisa e Extensão from UNICAMP (FAEPEX-UNICAMP, grant no. 2266/20) and FAPERGS COVID19 20-2551-0000258-6. J.L.P.-M. was supported by the Brazilian National Council for Scientific and Technological Development, CNPq, grant no. 305628/2020-8.