Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms

Viviani Mendes de Almeida; Daiane F Engel; Mayra F Ricci; Clênio Silva Cruz; Ícaro Santos Lopes; Daniele Almeida Alves; Mirna d' Auriol; João Magalhães; Elayne C Machado; Victor M Rocha; Toniana G Carvalho; Larisse S B Lacerda; Jordane C Pimenta; Mariana Aganetti; Giuliana S Zuccoli; Bradley J Smith; Victor C Carregari; Erika da Silva Rosa; Izabela Galvão; Geovanni Dantas Cassali; Cristiana C Garcia; Mauro Martins Teixeira; Leiliane C André; Fabiola Mara Ribeiro; Flaviano S Martins; Rafael Simone Saia; Vivian Vasconcelos Costa; Daniel Martins-de-Souza; Philip M Hansbro; João Trindade Marques; Eric R G R Aguiar; Angélica T Vieira

doi:10.1080/19490976.2023.2249146

Gut microbiota from patients with COVID-19 cause alterations in mice that resemble post-COVID symptoms

Gut Microbes. 2023 Dec;15(2):2249146. doi: 10.1080/19490976.2023.2249146.

Authors

Viviani Mendes de Almeida¹, Daiane F Engel², Mayra F Ricci¹, Clênio Silva Cruz¹, Ícaro Santos Lopes³, Daniele Almeida Alves⁴, Mirna d' Auriol⁵, João Magalhães¹, Elayne C Machado¹, Victor M Rocha¹, Toniana G Carvalho⁶, Larisse S B Lacerda⁷, Jordane C Pimenta⁷, Mariana Aganetti¹, Giuliana S Zuccoli⁸, Bradley J Smith⁸, Victor C Carregari⁸, Erika da Silva Rosa¹, Izabela Galvão¹, Geovanni Dantas Cassali⁹, Cristiana C Garcia¹⁰, Mauro Martins Teixeira⁷, Leiliane C André⁵, Fabiola Mara Ribeiro⁶, Flaviano S Martins¹¹, Rafael Simone Saia¹², Vivian Vasconcelos Costa⁷, Daniel Martins-de-Souza^{8

13

14

15}, Philip M Hansbro¹⁶, João Trindade Marques^{4

17}, Eric R G R Aguiar³, Angélica T Vieira¹

Affiliations

¹ Laboratory of Microbiota and Immunomodulation - Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, Brazil.
² Department of Clinical Analysis, School of Pharmacy, Universidade Federal de Ouro Preto - UFOP, Ouro Preto, Brazil.
³ Laboratory of Virus Bioinformatics - Department of Biological Science, Center of Biotechnology and Genetics, Universidade Estadual de Santa Cruz - UESC, Ilhéus, Brazil.
⁴ Laboratory of RNA Interference and Antiviral Immunity - Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, Brazil.
⁵ Laboratory of Toxicology - Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, Brazil.
⁶ Laboratory of Neurobiochemistry - Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, Brazil.
⁷ Center for Research and Development of Drugs - Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, Brazil.
⁸ Laboratory of Neuroproteomics - Department of Biochemistry and Tissue Biology, Institute of Biology, Universidade do Estado de Campinas - UNICAMP, Campinas, Brazil.
⁹ Laboratory of Comparative Pathology - Department of Pathology, Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, Brazil.
¹⁰ Laboratory of Respiratory Viruses and Measles, Instituto Oswaldo Cruz - Fiocruz, Rio de Janeiro, Brazil.
¹¹ Laboratory of Biotherapeutic Agents - Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais - UFMG, Belo Horizonte, Brazil.
¹² Laboratory of Intestinal Physiology - Department of Physiology, Ribeirão Preto Medical School, Universidade de São Paulo, Ribeirão Preto, Brazil.
¹³ D'Or Institute for Research and Education, São Paulo, Brazil.
¹⁴ Experimental Medicine Research Cluster, Universidade do Estado de Campinas - UNICAMP, Campinas, Brazil.
¹⁵ National Institute of Biomarkers in Neuropsychiatry, National Council for Scientific and Technological Development, São Paulo, Brazil.
¹⁶ Centre for Inflammation, Centenary Institute and University of Technology Sydney, Sydney, Australia.
¹⁷ CNRS UPR9022, University of Strasbourg, Strasbourg, France.

Abstract

Long-term sequelae of coronavirus disease (COVID)-19 are frequent and of major concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects the host gut microbiota, which is linked to disease severity in patients with COVID-19. Here, we report that the gut microbiota of post-COVID subjects had a remarkable predominance of Enterobacteriaceae strains with an antibiotic-resistant phenotype compared to healthy controls. Additionally, short-chain fatty acid (SCFA) levels were reduced in feces. Fecal transplantation from post-COVID subjects to germ-free mice led to lung inflammation and worse outcomes during pulmonary infection by multidrug-resistant Klebsiella pneumoniae. transplanted mice also exhibited poor cognitive performance. Overall, we show prolonged impacts of SARS-CoV-2 infection on the gut microbiota that persist after subjects have cleared the virus. Together, these data demonstrate that the gut microbiota can directly contribute to post-COVID sequelae, suggesting that it may be a potential therapeutic target.

Keywords: COVID-19; SARS-CoV-2; antimicrobial-resistance; inflammation; microbiota; post-COVID.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents
COVID-19*
Disease Progression
Gastrointestinal Microbiome*
Mice
SARS-CoV-2

Substances

Anti-Bacterial Agents

Grants and funding

This work was supported by the National Council for Scientific and Technological Development – CNPq (call MCTIC/CNPq/FNDCT/MS/SCTIE/Decit 07/2020 [process number: 402530/2020-9], Universal MCTIC/CNPq [process number: 408703/2021-0]), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) (APQ-03328-18; APQ-00686-21; Rede Mineira de Investigação em Mucosas e Pele 0096-22), and Instituto Serrapilheira (No. 03/2019).Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil (CAPES) Finance Code 001: V.M.A and D.A.A.CAPES-Print: I.G.Pró-Reitoria de Pesquisa da Universidade Federal de Minas Gerais – PRPq/UFMGSão Paulo Research Foundation (grants 2017/25588-1, 2018/14666-4, 2019/00098-7, 2019/05155-9 and 2020/04746-0): R.S.S. and D.M.S.National Health and Medical Research Council of Australia (105,9238, 1175134, 2010287): P.M.M.