Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants

Abstract Preterm infants (<37 weeks’ gestation) are commonly given broad-spectrum antibiotics due to their risk of severe conditions like necrotising enterocolitis and sepsis. However, antibiotics can disrupt early-life gut microbiota development, potentially impairing gut immunity and colonisati...

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Main Authors: Raymond Kiu, Elizabeth M. Darby, Cristina Alcon-Giner, Antia Acuna-Gonzalez, Anny Camargo, Lisa E. Lamberte, Sarah Phillips, Kathleen Sim, Alexander G. Shaw, Paul Clarke, Willem van Schaik, J. Simon Kroll, Lindsay J. Hall
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-62584-2
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author Raymond Kiu
Elizabeth M. Darby
Cristina Alcon-Giner
Antia Acuna-Gonzalez
Anny Camargo
Lisa E. Lamberte
Sarah Phillips
Kathleen Sim
Alexander G. Shaw
Paul Clarke
Willem van Schaik
J. Simon Kroll
Lindsay J. Hall
author_facet Raymond Kiu
Elizabeth M. Darby
Cristina Alcon-Giner
Antia Acuna-Gonzalez
Anny Camargo
Lisa E. Lamberte
Sarah Phillips
Kathleen Sim
Alexander G. Shaw
Paul Clarke
Willem van Schaik
J. Simon Kroll
Lindsay J. Hall
author_sort Raymond Kiu
collection DOAJ
description Abstract Preterm infants (<37 weeks’ gestation) are commonly given broad-spectrum antibiotics due to their risk of severe conditions like necrotising enterocolitis and sepsis. However, antibiotics can disrupt early-life gut microbiota development, potentially impairing gut immunity and colonisation resistance. Probiotics (e.g., certain Bifidobacterium strains) may help restore a healthy gut microbiota. In this study, we investigated the effects of probiotics and antibiotics on the gut microbiome and resistome in two unique cohorts of 34 very-low-birth-weight, human-milk-fed preterm infants - one of which received probiotics. Within each group, some infants received antibiotics (benzylpenicillin and/or gentamicin), while others did not. Using shotgun metagenomic sequencing on 92 longitudinal faecal samples, we reconstructed >300 metagenome-assembled genomes and obtained ~90 isolate genomes via targeted culturomics, allowing strain-level analysis. We also assessed ex vivo horizontal gene transfer (HGT) capacity of multidrug-resistant (MDR) Enterococcus using neonatal gut models. Here we show that probiotic supplementation significantly reduced antibiotic resistance gene prevalence, MDR pathogen load, and restored typical early-life microbiota profile. However, persistent MDR pathogens like Enterococcus, with high HGT potential, underscore the need for continued surveillance. Our findings underscore the complex interplay between antibiotics, probiotics, and HGT in shaping the neonatal microbiome and support further research into probiotics for antimicrobial stewardship in preterm populations.
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spelling doaj-art-5d1ef818ce164381b4de46dccf1a47db2025-08-20T04:03:06ZengNature PortfolioNature Communications2041-17232025-08-0116111610.1038/s41467-025-62584-2Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infantsRaymond Kiu0Elizabeth M. Darby1Cristina Alcon-Giner2Antia Acuna-Gonzalez3Anny Camargo4Lisa E. Lamberte5Sarah Phillips6Kathleen Sim7Alexander G. Shaw8Paul Clarke9Willem van Schaik10J. Simon Kroll11Lindsay J. Hall12Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamDepartment of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamFood, Microbiome and Health, Quadram Institute Bioscience, Norwich Research ParkFood, Microbiome and Health, Quadram Institute Bioscience, Norwich Research ParkFood, Microbiome and Health, Quadram Institute Bioscience, Norwich Research ParkInstitute of Microbiology and Infection, University of BirminghamFood, Microbiome and Health, Quadram Institute Bioscience, Norwich Research ParkFaculty of Medicine, Imperial College LondonFaculty of Medicine, Imperial College LondonNorfolk and Norwich University HospitalDepartment of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamFaculty of Medicine, Imperial College LondonDepartment of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of BirminghamAbstract Preterm infants (<37 weeks’ gestation) are commonly given broad-spectrum antibiotics due to their risk of severe conditions like necrotising enterocolitis and sepsis. However, antibiotics can disrupt early-life gut microbiota development, potentially impairing gut immunity and colonisation resistance. Probiotics (e.g., certain Bifidobacterium strains) may help restore a healthy gut microbiota. In this study, we investigated the effects of probiotics and antibiotics on the gut microbiome and resistome in two unique cohorts of 34 very-low-birth-weight, human-milk-fed preterm infants - one of which received probiotics. Within each group, some infants received antibiotics (benzylpenicillin and/or gentamicin), while others did not. Using shotgun metagenomic sequencing on 92 longitudinal faecal samples, we reconstructed >300 metagenome-assembled genomes and obtained ~90 isolate genomes via targeted culturomics, allowing strain-level analysis. We also assessed ex vivo horizontal gene transfer (HGT) capacity of multidrug-resistant (MDR) Enterococcus using neonatal gut models. Here we show that probiotic supplementation significantly reduced antibiotic resistance gene prevalence, MDR pathogen load, and restored typical early-life microbiota profile. However, persistent MDR pathogens like Enterococcus, with high HGT potential, underscore the need for continued surveillance. Our findings underscore the complex interplay between antibiotics, probiotics, and HGT in shaping the neonatal microbiome and support further research into probiotics for antimicrobial stewardship in preterm populations.https://doi.org/10.1038/s41467-025-62584-2
spellingShingle Raymond Kiu
Elizabeth M. Darby
Cristina Alcon-Giner
Antia Acuna-Gonzalez
Anny Camargo
Lisa E. Lamberte
Sarah Phillips
Kathleen Sim
Alexander G. Shaw
Paul Clarke
Willem van Schaik
J. Simon Kroll
Lindsay J. Hall
Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants
Nature Communications
title Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants
title_full Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants
title_fullStr Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants
title_full_unstemmed Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants
title_short Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants
title_sort impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very low birth weight preterm infants
url https://doi.org/10.1038/s41467-025-62584-2
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