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ToolsKiu, Raymond, Darby, Elizabeth M., Alcon-Giner, Cristina, Acuna-Gonzalez, Antia, Camargo, Anny, Lamberte, Lisa E., Phillips, Sarah, Sim, Kathleen, Shaw, Alexander G., Clarke, Paul, van Schaik, Willem, Kroll, J. Simon and Hall, Lindsay J. (2025) Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants. Nature Communications, 16. ISSN 2041-1723
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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.
| Item Type: | Article |
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| Additional Information: | Data availability: Infant faecal sample metagenome sequencing raw reads generated in this study have been deposited in the NCBI Sequence Read Archive (SRA) under accession no. PRJNA1191223. Sequencing raw reads and draft genome assemblies for 89 isolates generated in this study have been deposited in the NCBI SRA and GenBank respectively, under accession no. PRJNA119225. Sequencing raw reads and draft genome assemblies from long-read WGS in Enterococcus plasmid transfer study are available in SRA (for raw sequencing reads) and GenBank (genome assemblies) respectively under accession no. PRJNA119226. Source data (also provided with this paper) and all 322 metagenome-assembled genomes recovered from gut metagenome samples are available via GitHub repository (https://github.com/raymondkiu/Infant-Resistome-Study) and Zenodo (https://doi.org/10.5281/zenodo.15975760). Source data are provided with this paper. Code availability: No custom software was developed for this study. All analyses were performed using existing software and tools as described in the Methods. Acknowledgements: This research was supported in part by the Norwich Bioscience Institutes (NBI) Research Computing through the provision of a high performance computing cluster. We would like to thank the DNA sequencing teams at both Wellcome Trust Sanger Institute and Quadram Institute Bioscience for performing genomic DNA sequencing for this study. This work was funded via Wellcome Trust Investigator Awar’sd to L.J.H. (100974/C/13/Z and 220540/Z/20/A) and support of the BBSRC Norwich Research Park Bioscience Doctoral Training Grant (BB/M011216/1; supervisor, L.J.H.; student, C.A.G.), Institute Strategic Programme (ISP) grant for Gut Microbes and Health BB/R012490/1 and its constituent project(s), BBS/E/F/000PR10353 and BBS/E/F/000PR10355 and a BBSRC ISP Food, Microbiome and Health BB/X011054/1 and its constituent project BBS/E/QU/230001B to L.J.H. W.v.S and L.J.H were also supported by BBSRC grant BB/S017941/1, and current funding by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit in Public Health Genomics, a partnership between the UK Health Security Agency and the University of Birmingham. The views expressed are those of the author(s) and not necessarily those of the NIHR, the UK Health Security Agency or the Department of Health and Social Care. Work at Imperial Healthcare NICUs was supported by a programme grant from the Winnicott Foundation to J.S.K. and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial Healthcare NHS Trust and Imperial College London. K.S. was funded by an NIHR Doctoral Research Fellowship (NIHR-DRF-2011-04-128). We sincerely thank all clinical nurses at NNUH and Imperial Healthcare NICUs for collecting stool samples. We would like to give a special mention to research nurses Karen Few, Hayley Aylmer, and Zoe McClure for obtaining consent from parents and collecting samples. |
| Uncontrolled Keywords: | chemistry(all),biochemistry, genetics and molecular biology(all),general,physics and astronomy(all),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1600 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 18 Sep 2025 08:31 |
| Last Modified: | 18 Oct 2025 15:31 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/100430 |
| DOI: | 10.1038/s41467-025-62584-2 |
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