Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants
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Objectives: In 2014 probiotic supplementation (Lactobacillus acidophilus and Bifidobacterium. longum subspecies infantis; Infloran ®) was introduced as standard of care to prevent necrotizing enterocolitis (NEC) in extremely preterm infants in Norway. We aimed to evaluate the influence of probiotics and antibiotic therapy on the developing gut microbiota and antibiotic resistome. Study design: A prospective, observational multicenter study in six tertiary-care neonatal units. We enrolled 76 infants; 31 probiotic-supplemented extremely preterm infants < 28 weeks gestation, 35 very preterm infants 28-31 weeks gestation not given probiotics and 10 healthy full-term control infants. Taxonomic composition and collection of antibiotic resistance genes (resistome) in fecal samples, collected at 7 and 28 days and 4 months age, were analyzed using shotgun metagenome sequencing. Results: Mean (SD) birth weight was 825 (178) g and 1290 (220) g in preterm infants exposed and not exposed to probiotics, respectively. Two extremely preterm infants receiving probiotic developed NEC. At 7 days age we found higher median relative abundance of Bifidobacterium in probiotic supplemented infants (64.7%) compared to non-supplemented preterm infants (0.0%) and term control infants (43.9%). Lactobacillus was only detected in small amounts in all groups, but the relative abundance increased up to 4 months. Extremely preterm infants receiving probiotics had also much higher antibiotic exposure, still overall microbial diversity and resistome was not different than in more mature infants at 4 weeks and 4 months. Conclusion: Probiotic supplementation may induce colonization resistance and alleviate harmful effects of antibiotics on the gut microbiota and antibiotic resistome. The early high abundance of Bifidobacterium in probiotic-supplemented extremely preterm infants may suggest that a gradual increase in supplementation is warranted. Clinical Trial Registration: Clinicaltrials.gov: NCT02197468. https://clinicaltrials.gov/ct2/show/NCT02197468
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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 [32]
The Results (Taxonomic composition; page not provided) identify these genera in preterm infants’ fecal microbiota, and the Discussion (page not provided) mentions sepsis caused by Gram-negative bacteria generally. Neither passage identifies Enterococcus, Escherichia, and Klebsiella as common nosocomial pathogens or links them to late-onset infections. Searches for “nosocomial” and “late-onset” found no passage making that link. (LLM, conf=0.75)
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References 66 · Cited by 102
- Authors
- Esaiassen, E., Hjerde, E., Cavanagh, J. P., Pedersen, T., Andresen, J. H., Rettedal, S. I., Støen, R., Nakstad, B., Willassen, N. P., & Klingenberg, C.
- Affiliations
- University Hospital of North Norway (NO)
- UiT The Arctic University of Norway (NO)
- Haukeland University Hospital (NO)
- Oslo University Hospital (NO)
- Stavanger University Hospital (NO)
- Norwegian University of Science and Technology (NO)
- University of Oslo (NO)
- Corresponding author
- Klingenberg, Claus
- ORCID
- Venue
- Frontiers in Pediatrics
- Publisher
- Frontiers Media SA
- Published
- 2018-11-16
- Volume
- 6
- Pages
- 347-347
- ISSN
- 2296-2360 (ISSN-L)
- PMC
- PMC6250747
- OpenAlex
- W2901088447
- Cited by
- 102
- References
- 66
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 14 · 2023: 15 · 2022: 18 · 2021: 23 · 2020: 11 · 2019: 4
- FWCI
- 7.86
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Pediatrics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Universitetet i Tromsø
- Helse Nord RHF
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- probiotic supplementation, preterm infants, gut microbiota, antibiotic resistome, antibiotic resistance genes, necrotizing enterocolitis, Bifidobacterium, Lactobacillus, colonization resistance, neonatal antibiotic exposure, extremely preterm infants, very preterm infants, fecal microbiota
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