Absence of gut microbiota restoration following meropenem treatment in a systemic infection model

Abstract Antibiotics have been shown to have unintended effects on the host by disrupting the beneficial microbiota. In this study, we explored and longitudinally monitored microbiota during and after antibiotic treatment for infection. We induced a systemic Escherichia coli infection in 45 BALB/c m...

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Main Authors: Filipe Moura Ribeiro, Camila Fontoura Acosta Ribeiro, Elizabete de Souza Cândido, Danieli Fernanda Buccini, Marlon Henrique Cardoso, Gislaine Greice de Oliveira Silva Silveira, Carolina Moura de Souza, Osmar Nascimento Silva, Gisele Braziliano de Andrade, Alanderson Rodrigues da Silva, Franciele Bathel da Mota, Sarah Saory Makimoto, Rosangela dos Santos Ferreira, Nathália Cavichiolli de Oliveira, Alinne Pereira de Castro, Cristiano Marcelo Espínola Carvalho, Cesar de la Fuente-Nunez, Octávio Luiz Franco
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:npj Antimicrobials and Resistance
Online Access:https://doi.org/10.1038/s44259-025-00129-9
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author Filipe Moura Ribeiro
Camila Fontoura Acosta Ribeiro
Elizabete de Souza Cândido
Danieli Fernanda Buccini
Marlon Henrique Cardoso
Gislaine Greice de Oliveira Silva Silveira
Carolina Moura de Souza
Osmar Nascimento Silva
Gisele Braziliano de Andrade
Alanderson Rodrigues da Silva
Franciele Bathel da Mota
Sarah Saory Makimoto
Rosangela dos Santos Ferreira
Nathália Cavichiolli de Oliveira
Alinne Pereira de Castro
Cristiano Marcelo Espínola Carvalho
Cesar de la Fuente-Nunez
Octávio Luiz Franco
author_facet Filipe Moura Ribeiro
Camila Fontoura Acosta Ribeiro
Elizabete de Souza Cândido
Danieli Fernanda Buccini
Marlon Henrique Cardoso
Gislaine Greice de Oliveira Silva Silveira
Carolina Moura de Souza
Osmar Nascimento Silva
Gisele Braziliano de Andrade
Alanderson Rodrigues da Silva
Franciele Bathel da Mota
Sarah Saory Makimoto
Rosangela dos Santos Ferreira
Nathália Cavichiolli de Oliveira
Alinne Pereira de Castro
Cristiano Marcelo Espínola Carvalho
Cesar de la Fuente-Nunez
Octávio Luiz Franco
author_sort Filipe Moura Ribeiro
collection DOAJ
description Abstract Antibiotics have been shown to have unintended effects on the host by disrupting the beneficial microbiota. In this study, we explored and longitudinally monitored microbiota during and after antibiotic treatment for infection. We induced a systemic Escherichia coli infection in 45 BALB/c mice, with 25 as uninfected controls. The disease was treated with meropenem. The animals were evaluated longitudinally three times, including 3 hours, five days of treatment, and 30 days post-treatment. Intestinal, lung, blood, and peritoneal lavage samples were collected for analysis. Our findings show that meropenem effectively treated the lethal systemic infection caused by E. coli. Hematological parameters, crypt depth, and goblet cell numbers remained unchanged for 30 days post-antibiotic treatment. However, antibiotic treatment impaired the recovery of the gut microbiota, even 30 days post-treatment. This long-term meropenem impact on microbiota was observed in both infected and non-infected (saline-treated) groups. Alpha and beta diversity analyses did not indicate a microbiota recovery. Notably, Lactobacillus and Bacteroides decreased, while Clostridioides, Enterococcus, and Escherichia-Shigella increased. This study provides novel evidence that, even 30 days after meropenem treatment in a simulated E. coli infection, the intestinal microbiota does not recover, highlighting prolonged antibiotic-induced dysbiosis.
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spelling doaj-art-e0c4752830844eab957899cef998344a2025-08-20T03:42:00ZengNature Portfolionpj Antimicrobials and Resistance2731-87452025-06-013111210.1038/s44259-025-00129-9Absence of gut microbiota restoration following meropenem treatment in a systemic infection modelFilipe Moura Ribeiro0Camila Fontoura Acosta Ribeiro1Elizabete de Souza Cândido2Danieli Fernanda Buccini3Marlon Henrique Cardoso4Gislaine Greice de Oliveira Silva Silveira5Carolina Moura de Souza6Osmar Nascimento Silva7Gisele Braziliano de Andrade8Alanderson Rodrigues da Silva9Franciele Bathel da Mota10Sarah Saory Makimoto11Rosangela dos Santos Ferreira12Nathália Cavichiolli de Oliveira13Alinne Pereira de Castro14Cristiano Marcelo Espínola Carvalho15Cesar de la Fuente-Nunez16Octávio Luiz Franco17Centro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de BrasíliaS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoCentro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de BrasíliaS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoUniEvangélica, Universidade Evangélica de GoiásS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoS-Inova Biotech, Programa de Pós-Graduação em Biotecnologia, Universidade Católica Dom BoscoMachine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of PennsylvaniaCentro de Análises Proteômicas e Bioquímicas, Programa de Pós-Graduação em Ciências Genômicas e Biotecnologia, Universidade Católica de BrasíliaAbstract Antibiotics have been shown to have unintended effects on the host by disrupting the beneficial microbiota. In this study, we explored and longitudinally monitored microbiota during and after antibiotic treatment for infection. We induced a systemic Escherichia coli infection in 45 BALB/c mice, with 25 as uninfected controls. The disease was treated with meropenem. The animals were evaluated longitudinally three times, including 3 hours, five days of treatment, and 30 days post-treatment. Intestinal, lung, blood, and peritoneal lavage samples were collected for analysis. Our findings show that meropenem effectively treated the lethal systemic infection caused by E. coli. Hematological parameters, crypt depth, and goblet cell numbers remained unchanged for 30 days post-antibiotic treatment. However, antibiotic treatment impaired the recovery of the gut microbiota, even 30 days post-treatment. This long-term meropenem impact on microbiota was observed in both infected and non-infected (saline-treated) groups. Alpha and beta diversity analyses did not indicate a microbiota recovery. Notably, Lactobacillus and Bacteroides decreased, while Clostridioides, Enterococcus, and Escherichia-Shigella increased. This study provides novel evidence that, even 30 days after meropenem treatment in a simulated E. coli infection, the intestinal microbiota does not recover, highlighting prolonged antibiotic-induced dysbiosis.https://doi.org/10.1038/s44259-025-00129-9
spellingShingle Filipe Moura Ribeiro
Camila Fontoura Acosta Ribeiro
Elizabete de Souza Cândido
Danieli Fernanda Buccini
Marlon Henrique Cardoso
Gislaine Greice de Oliveira Silva Silveira
Carolina Moura de Souza
Osmar Nascimento Silva
Gisele Braziliano de Andrade
Alanderson Rodrigues da Silva
Franciele Bathel da Mota
Sarah Saory Makimoto
Rosangela dos Santos Ferreira
Nathália Cavichiolli de Oliveira
Alinne Pereira de Castro
Cristiano Marcelo Espínola Carvalho
Cesar de la Fuente-Nunez
Octávio Luiz Franco
Absence of gut microbiota restoration following meropenem treatment in a systemic infection model
npj Antimicrobials and Resistance
title Absence of gut microbiota restoration following meropenem treatment in a systemic infection model
title_full Absence of gut microbiota restoration following meropenem treatment in a systemic infection model
title_fullStr Absence of gut microbiota restoration following meropenem treatment in a systemic infection model
title_full_unstemmed Absence of gut microbiota restoration following meropenem treatment in a systemic infection model
title_short Absence of gut microbiota restoration following meropenem treatment in a systemic infection model
title_sort absence of gut microbiota restoration following meropenem treatment in a systemic infection model
url https://doi.org/10.1038/s44259-025-00129-9
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