Development of early life gut resistome and mobilome across gestational ages and microbiota-modifying treatments
Open accessAbstract
BACKGROUND: Gestational age (GA) and associated level of gastrointestinal tract maturation are major factors driving the initial gut microbiota composition in preterm infants. Besides, compared to term infants, premature infants often receive antibiotics to treat infections and probiotics to restore optimal gut microbiota. How GA, antibiotics, and probiotics modulate the microbiota's core characteristics, gut resistome and mobilome, remains nascent. METHODS: We analysed metagenomic data from a longitudinal observational study in six Norwegian neonatal intensive care units to describe the bacterial microbiota of infants of varying GA and receiving different treatments. The cohort consisted of probiotic-supplemented and antibiotic-exposed extremely preterm infants (n = 29), antibiotic-exposed very preterm (n = 25), antibiotic-unexposed very preterm (n = 8), and antibiotic-unexposed full-term (n = 10) infants. The stool samples were collected on days of life 7, 28, 120, and 365, and DNA extraction was followed by shotgun metagenome sequencing and bioinformatical analysis. FINDINGS: The top predictors of microbiota maturation were hospitalisation length and GA. Probiotic administration rendered the gut microbiota and resistome of extremely preterm infants more alike to term infants on day 7 and ameliorated GA-driven loss of microbiota interconnectivity and stability. GA, hospitalisation, and both microbiota-modifying treatments (antibiotics and probiotics) contributed to an elevated carriage of mobile genetic elements in preterm infants compared to term controls. Finally, Escherichia coli was associated with the highest number of antibiotic-resistance genes, followed by Klebsiella pneumoniae and Klebsiella aerogenes. INTERPRETATION: Prolonged hospitalisation, antibiotics, and probiotic intervention contribute to dynamic alterations in resistome and mobilome, gut microbiota characteristics relevant to infection risk. FUNDING: Odd-Berg Group, Northern Norway Regional Health Authority.
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Enterococcus, Escherichia, and Klebsiella are common nosocomial pathogens and are often implicated in late-onset infections in preterm infants.
“These findings align with reports from other NICU studies, where Enterococcus, Escherichia, and Klebsiella are common nosocomial pathogens and are often implicated in late-onset infections in preterm infants32,45,46.”
From Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants. (2025) · cites this paper as [46]
The Discussion (page not available) reports high prevalence of E. coli, E. faecalis, and K. aerogenes in very preterm infants and says this gut composition has been linked to elevated sepsis risk. It does not establish that these genera are common nosocomial pathogens often responsible for late-onset infections; the Results (Cohort description, page not available) state that no preterm infant in this cohort developed sepsis. (LLM, conf=0.85)
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References 61 · Cited by 52
- Authors
- Bargheet, A., Klingenberg, C., Esaiassen, E., Hjerde, E., Cavanagh, J. P., Bengtsson-Palme, J., & Pettersen, V. K.
- Affiliations
- UiT The Arctic University of Norway (NO)
- University Hospital of North Norway (NO)
- Corresponding author
- Pettersen, Veronika Kuchařová
- ORCID
- Venue
- eBioMedicine
- Publisher
- Elsevier BV
- Published
- 2023-06
- Volume
- 92
- Pages
- 104613
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC10192547
- OpenAlex
- W4376626774
- Cited by
- 52
- References
- 61
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 18 · 2023: 4
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EBioMedicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Haukeland Universitetssjukehus
- St. Olavs Hospital Universitetssykehuset i Trondheim
- Centre for Antibiotic Resistance Research, University of Gothenburg
- Tromsø Forskningsstiftelse (18_CANS_AS)
- Knut och Alice Wallenbergs Stiftelse (KAW 2020.0239)
- Stiftelsen för Strategisk Forskning (FFL21-0174)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
- Keywords
- gut resistome, gut microbiota maturation, gestational age, preterm infants, extremely preterm infants, very preterm infants, probiotics, antibiotics, mobile genetic elements, antibiotic resistance genes, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, neonatal intensive care, length of hospital stay, infection risk
- MeSH terms
- Anti-Bacterial Agents, Feces, Gestational Age, Humans, Infant, Infant, Newborn, Probiotics, Gastrointestinal Tract, Infant, Extremely Premature, Microbiota
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