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The infant gut resistome is associated with E. coli and early-life exposures
BACKGROUND: The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood. We investigated the early-life exposures and taxonomic signatures ass...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252198/ https://www.ncbi.nlm.nih.gov/pubmed/34215179 http://dx.doi.org/10.1186/s12866-021-02129-x |
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author | Lebeaux, Rebecca M. Coker, Modupe O. Dade, Erika F. Palys, Thomas J. Morrison, Hilary G. Ross, Benjamin D. Baker, Emily R. Karagas, Margaret R. Madan, Juliette C. Hoen, Anne G. |
author_facet | Lebeaux, Rebecca M. Coker, Modupe O. Dade, Erika F. Palys, Thomas J. Morrison, Hilary G. Ross, Benjamin D. Baker, Emily R. Karagas, Margaret R. Madan, Juliette C. Hoen, Anne G. |
author_sort | Lebeaux, Rebecca M. |
collection | PubMed |
description | BACKGROUND: The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling were used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs. RESULTS: Metagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks’ gestation) and 15 late preterm (33–36 weeks’ gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54–5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux. The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically Escherichia coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a trend towards a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97–1.29)] as well as having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12–1.84)] at 1 year compared to infants born vaginally. CONCLUSIONS: Our findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the risk of antibiotic resistant infections. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-021-02129-x. |
format | Online Article Text |
id | pubmed-8252198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-82521982021-07-06 The infant gut resistome is associated with E. coli and early-life exposures Lebeaux, Rebecca M. Coker, Modupe O. Dade, Erika F. Palys, Thomas J. Morrison, Hilary G. Ross, Benjamin D. Baker, Emily R. Karagas, Margaret R. Madan, Juliette C. Hoen, Anne G. BMC Microbiol Research Article BACKGROUND: The human gut microbiome harbors a collection of bacterial antimicrobial resistance genes (ARGs) known as the resistome. The factors associated with establishment of the resistome in early life are not well understood. We investigated the early-life exposures and taxonomic signatures associated with resistome development over the first year of life in a large, prospective cohort in the United States. Shotgun metagenomic sequencing was used to profile both microbial composition and ARGs in stool samples collected at 6 weeks and 1 year of age from infants enrolled in the New Hampshire Birth Cohort Study. Negative binomial regression and statistical modeling were used to examine infant factors such as sex, delivery mode, feeding method, gestational age, antibiotic exposure, and infant gut microbiome composition in relation to the diversity and relative abundance of ARGs. RESULTS: Metagenomic sequencing was performed on paired samples from 195 full term (at least 37 weeks’ gestation) and 15 late preterm (33–36 weeks’ gestation) infants. 6-week samples compared to 1-year samples had 4.37 times (95% CI: 3.54–5.39) the rate of harboring ARGs. The majority of ARGs that were at a greater relative abundance at 6 weeks (chi-squared p < 0.01) worked through the mechanism of antibiotic efflux. The overall relative abundance of the resistome was strongly correlated with Proteobacteria (Spearman correlation = 78.9%) and specifically Escherichia coli (62.2%) relative abundance in the gut microbiome. Among infant characteristics, delivery mode was most strongly associated with the diversity and relative abundance of ARGs. Infants born via cesarean delivery had a trend towards a higher risk of harboring unique ARGs [relative risk = 1.12 (95% CI: 0.97–1.29)] as well as having an increased risk for overall ARG relative abundance [relative risk = 1.43 (95% CI: 1.12–1.84)] at 1 year compared to infants born vaginally. CONCLUSIONS: Our findings suggest that the developing infant gut resistome may be alterable by early-life exposures. Establishing the extent to which infant characteristics and early-life exposures impact the resistome can ultimately lead to interventions that decrease the transmission of ARGs and thus the risk of antibiotic resistant infections. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12866-021-02129-x. BioMed Central 2021-07-02 /pmc/articles/PMC8252198/ /pubmed/34215179 http://dx.doi.org/10.1186/s12866-021-02129-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Lebeaux, Rebecca M. Coker, Modupe O. Dade, Erika F. Palys, Thomas J. Morrison, Hilary G. Ross, Benjamin D. Baker, Emily R. Karagas, Margaret R. Madan, Juliette C. Hoen, Anne G. The infant gut resistome is associated with E. coli and early-life exposures |
title | The infant gut resistome is associated with E. coli and early-life exposures |
title_full | The infant gut resistome is associated with E. coli and early-life exposures |
title_fullStr | The infant gut resistome is associated with E. coli and early-life exposures |
title_full_unstemmed | The infant gut resistome is associated with E. coli and early-life exposures |
title_short | The infant gut resistome is associated with E. coli and early-life exposures |
title_sort | infant gut resistome is associated with e. coli and early-life exposures |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252198/ https://www.ncbi.nlm.nih.gov/pubmed/34215179 http://dx.doi.org/10.1186/s12866-021-02129-x |
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