Metagenomics analysis of the neonatal intestinal resistome

Stefano Leo; Omer F Cetiner; Laure F Pittet; Nicole L Messina; William Jakob; Laurent Falquet; Nigel Curtis; Petra Zimmermann

doi:10.3389/fped.2023.1169651

Metagenomics analysis of the neonatal intestinal resistome

Front Pediatr. 2023 Jun 16:11:1169651. doi: 10.3389/fped.2023.1169651. eCollection 2023.

Authors

Stefano Leo^{1

2}, Omer F Cetiner³, Laure F Pittet^{4

5

6}, Nicole L Messina^{4

5}, William Jakob⁷, Laurent Falquet⁸, Nigel Curtis^{4

5

9}, Petra Zimmermann^{1

2

4

5}

Affiliations

¹ Department for Community Health, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
² Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland.
³ Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.
⁴ Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
⁵ Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, VIC, Australia.
⁶ Pediatric Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
⁷ Microbiology Laboratory, Fribourg Hospital, Fribourg, Switzerland.
⁸ Department of Biology, University of Fribourg and Swiss Institute of Bioinformatics, Fribourg, Switzerland.
⁹ Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, VIC, Australia.

Abstract

Introduction: The intestinal microbiome forms a major reservoir for antibiotic resistance genes (ARGs). Little is known about the neonatal intestinal resistome.

Objective: The objective of this study was to investigate the intestinal resistome and factors that influence the abundance of ARGs in a large cohort of neonates.

Methods: Shotgun metagenomics was used to analyse the resistome in stool samples collected at 1 week of age from 390 healthy, term-born neonates who did not receive antibiotics.

Results: Overall, 913 ARGs belonging to 27 classes were identified. The most abundant ARGs were those conferring resistance to tetracyclines, quaternary ammonium compounds, and macrolide-lincosamide-streptogramin-B. Phylogenetic composition was strongly associated with the resistome composition. Other factors that were associated with the abundance of ARGs were delivery mode, gestational age, birth weight, feeding method, and antibiotics in the last trimester of pregnancy. Sex, ethnicity, probiotic use during pregnancy, and intrapartum antibiotics had little effect on the abundance of ARGs.

Conclusion: Even in the absence of direct antibiotic exposure, the neonatal intestine harbours a high abundance and a variety of ARGs.

Keywords: antibiotic resistance; gut; infant; microbiome; microbiota; mobilome; stool.

Grants and funding

This work was supported by the Australian National Health and Medical Research Council (NHMRC) (grant no. GNT1051228 and GNT1099680) and the Royal Children’s Hospital Foundation (grant no. RCHF 2019-1140). PZ is supported by grants from the Swiss National Foundation (grant no. PZPGP3_193140) and the University of Fribourg and the Fribourg Hospital, Switzerland. NC is supported by a National Health and Medical Research Council (NHMRC) Investigator Grant (grant no. GNT1197117). None of the funders had a role in designing the study or in the study conduct.