Asymptomatic gut colonization by extended-spectrum beta-lactamase-producing Escherichia coli is not associated with an altered gut microbiome or metabolome in Dutch adults
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
ABSTRACT Background Gut colonization by antibiotic resistant E. coli strains, including extended-spectrum beta-lactamase (ESBL)-producing E. coli is a risk factor for developing overt infection. The gut microbiome can provide colonization resistance against enteropathogens, but it remains unclear whether it confers resistance against potentially pathogenic ESBL-producing E. coli . Materials From a Dutch cross-sectional population study (PIENTER-3), feces from 2751 individuals were used to culture ESBL-producing bacteria. Of these, we selected 49 samples which were positive for an ESBL-producing Escherichia coli (ESBL + ), and negative for a variety of variables known to affect microbiome composition. These were matched in a 1:1 ratio to ESBL − samples based on age, sex, having been abroad in the past six months and ethnicity. Shotgun metagenomic sequencing was performed and taxonomic species composition and functional annotations (microbial metabolism and carbohydrate-active enzymes) were determined. Targeted quantitative metabolic profiling ( 1 H NMR-spectroscopy) was performed to investigate metabolomic profiles. Results No differences in alpha or beta diversity were observed, nor in relative abundance, between ESBL + and ESBL − individuals based on bacterial species level composition. Machine learning approaches based on microbiota composition did not accurately predict ESBL status (area under the receiver operating characteristic curve (AUROC)=0.53), neither when based on functional profiles. The metabolome did also not convincingly differ between ESBL groups as assessed by a variety of approaches, including machine learning through random forest (AUROC=0.61). Conclusion Using a combination of multi-omics and machine learning approaches, we conclude that asymptomatic gut carriage of ESBL-producing E. coli is not associated with an altered microbiome composition or function. This may suggest that microbiome-mediated colonization resistance against ESBL-producing E. coli is not as relevant as it is against other enteropathogens.
Authors 12
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Quinten R. Ducarmon corresponding Aachen Center for Microbiome Analyses and Therapeutics Department of Medical Microbiology Center for Microiome Analyses and Therapeutics Deprtment of Medicl Microbiology
Leiden University · Leiden University Medical Center
Affiliation as printed
Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Center for Microiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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Romy Daniëlle Zwittink Aachen Center for Microbiome Analyses and Therapeutics Department of Medical Microbiology Center for Microiome Analyses and Therapeutics Deprtment of Medicl Microbiology
Leiden University · Leiden University Medical Center
Affiliation as printed
Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Center for Microiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Amsterdam Medical Center, Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands
Department of Medial Mirobiology and Infetion Prevention, Amsterdam University Medial Centers, Amsterdam Medial Center, Amsterdam Infetion and Immunity Institute, Amsterdam, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
Center for Proteomics an Metabolomics, Leien University Meical Center, Leien, the Netherlans
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Sam Nooij Aachen Center for Microbiome Analyses and Therapeutics Department of Medical Microbiology Center for Microiome Analyses and Therapeutics Deprtment of Medicl Microbiology
Leiden University · Leiden University Medical Center
Affiliation as printed
Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Center for Microiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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National Institute for Public Health and the Environment
Affiliation as printed
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Cntr for Infctious Disas Control, National Institut for Public Halth and th Environmnt, Bilthovn, Th Nthrlands
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National Institute for Public Health and the Environment
Affiliation as printed
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Cntr for Infctious Disas Control, National Institut for Public Halth and th Environmnt, Bilthovn, Th Nthrlands
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National Institute for Public Health and the Environment
Affiliation as printed
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Cntr for Infctious Disas Control, National Institut for Public Halth and th Environmnt, Bilthovn, Th Nthrlands
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Leiden University Medical Center
Affiliation as printed
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands
Center for Proteomics an Metabolomics, Leien University Meical Center, Leien, the Netherlans
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Amsterdam University Medical Centers · University of Amsterdam
Affiliation as printed
Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Amsterdam Medical Center, Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands
Department of Medial Mirobiology and Infetion Prevention, Amsterdam University Medial Centers, Amsterdam Medial Center, Amsterdam Infetion and Immunity Institute, Amsterdam, the Netherlands
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National Institute for Public Health and the Environment
Affiliation as printed
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Cntr for Infctious Disas Control, National Institut for Public Halth and th Environmnt, Bilthovn, Th Nthrlands
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Ed J. Kuijper Aachen Center for Microbiome Analyses and Therapeutics Department of Medical Microbiology Center for Microiome Analyses and Therapeutics Deprtment of Medicl Microbiology
Leiden University · Leiden University Medical Center · National Institute for Public Health and the Environment
Affiliation as printed
Center for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
Center for Microbiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
Center for Microiome Analyses and Therapeutics, Leiden University Medical Center, Leiden, The Netherlands
Cntr for Infctious Disas Control, National Institut for Public Halth and th Environmnt, Bilthovn, Th Nthrlands
Deprtment of Medicl Microbiology, Leiden University Medicl Center, Leiden, The Netherlnds
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