Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection

ABSTRACT Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test thi...

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Autores principales:	Claire Roubaud-Baudron, Victoria E. Ruiz, Alexander M. Swan, Bruce A. Vallance, Ceren Ozkul, Zhiheng Pei, Jackie Li, Thomas W. Battaglia, Guillermo I. Perez-Perez, Martin J. Blaser
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Citrobacter rodentium pathogen-induced colitis gastrointestinal microbiota host resistance murine model bioluminescence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2c91dfe35c994798aec305fa5fefdb6b
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spelling	oai:doaj.org-article:2c91dfe35c994798aec305fa5fefdb6b2021-11-15T15:54:47ZLong-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection10.1128/mBio.02820-192150-7511https://doaj.org/article/2c91dfe35c994798aec305fa5fefdb6b2019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02820-19https://doaj.org/toc/2150-7511ABSTRACT Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test this hypothesis, C57BL/6 mice received a 5-day course of tylosin (macrolide), amoxicillin (β-lactam), or neither (control) early in life and were challenged with Citrobacter rodentium up to 80 days thereafter. The early-life antibiotic course led to persistent alterations in the intestinal microbiota and even with pathogen challenge 80 days later worsened the subsequent colitis. Compared to exposure to amoxicillin, exposure to tylosin led to greater disease severity and microbiota perturbation. Transferring the antibiotic-perturbed microbiota to germfree animals led to worsened colitis, indicating that the perturbed microbiota was sufficient for the increased disease susceptibility. These experiments highlight the long-term effects of early-life antibiotic exposure on susceptibility to acquired pathogens. IMPORTANCE The gastrointestinal microbiota protects hosts from enteric infections; while antibiotics, by altering the microbiota, may diminish this protection. We show that after early-life exposure to antibiotics host susceptibility to enhanced Citrobacter rodentium-induced colitis is persistent and that this enhanced disease susceptibility is transferable by the antibiotic-altered microbiota. These results strongly suggest that early-life antibiotics have long-term consequences on the gut microbiota and enteropathogen infection susceptibility.Claire Roubaud-BaudronVictoria E. RuizAlexander M. SwanBruce A. VallanceCeren OzkulZhiheng PeiJackie LiThomas W. BattagliaGuillermo I. Perez-PerezMartin J. BlaserAmerican Society for MicrobiologyarticleCitrobacter rodentiumpathogen-induced colitisgastrointestinal microbiotahost resistancemurine modelbioluminescenceMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Citrobacter rodentium pathogen-induced colitis gastrointestinal microbiota host resistance murine model bioluminescence Microbiology QR1-502
spellingShingle	Citrobacter rodentium pathogen-induced colitis gastrointestinal microbiota host resistance murine model bioluminescence Microbiology QR1-502 Claire Roubaud-Baudron Victoria E. Ruiz Alexander M. Swan Bruce A. Vallance Ceren Ozkul Zhiheng Pei Jackie Li Thomas W. Battaglia Guillermo I. Perez-Perez Martin J. Blaser Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection
description	ABSTRACT Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test this hypothesis, C57BL/6 mice received a 5-day course of tylosin (macrolide), amoxicillin (β-lactam), or neither (control) early in life and were challenged with Citrobacter rodentium up to 80 days thereafter. The early-life antibiotic course led to persistent alterations in the intestinal microbiota and even with pathogen challenge 80 days later worsened the subsequent colitis. Compared to exposure to amoxicillin, exposure to tylosin led to greater disease severity and microbiota perturbation. Transferring the antibiotic-perturbed microbiota to germfree animals led to worsened colitis, indicating that the perturbed microbiota was sufficient for the increased disease susceptibility. These experiments highlight the long-term effects of early-life antibiotic exposure on susceptibility to acquired pathogens. IMPORTANCE The gastrointestinal microbiota protects hosts from enteric infections; while antibiotics, by altering the microbiota, may diminish this protection. We show that after early-life exposure to antibiotics host susceptibility to enhanced Citrobacter rodentium-induced colitis is persistent and that this enhanced disease susceptibility is transferable by the antibiotic-altered microbiota. These results strongly suggest that early-life antibiotics have long-term consequences on the gut microbiota and enteropathogen infection susceptibility.
format	article
author	Claire Roubaud-Baudron Victoria E. Ruiz Alexander M. Swan Bruce A. Vallance Ceren Ozkul Zhiheng Pei Jackie Li Thomas W. Battaglia Guillermo I. Perez-Perez Martin J. Blaser
author_facet	Claire Roubaud-Baudron Victoria E. Ruiz Alexander M. Swan Bruce A. Vallance Ceren Ozkul Zhiheng Pei Jackie Li Thomas W. Battaglia Guillermo I. Perez-Perez Martin J. Blaser
author_sort	Claire Roubaud-Baudron
title	Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection
title_short	Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection
title_full	Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection
title_fullStr	Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection
title_full_unstemmed	Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection
title_sort	long-term effects of early-life antibiotic exposure on resistance to subsequent bacterial infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/2c91dfe35c994798aec305fa5fefdb6b
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Long-Term Effects of Early-Life Antibiotic Exposure on Resistance to Subsequent Bacterial Infection

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