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Effect of probiotic supplementation on the gut microbiota in very preterm infants: a systematic review
  1. Kayleigh Vievermanns1,
  2. Thomas H Dierikx1,2,
  3. Nathalie J Oldenburger1,
  4. Faridi S Jamaludin3,
  5. Hendrik J Niemarkt4,5,
  6. Tim G J de Meij1,6
  1. 1 Pediatric Gastroenterology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  2. 2 Microbiology, Maastricht UMC+, Maastricht, The Netherlands
  3. 3 Medical Library AMC, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
  4. 4 Neonatology, Maxima Medisch Centrum locatie Veldhoven, Veldhoven, The Netherlands
  5. 5 Electrical Engineering, TU Eindhoven, Eindhoven, The Netherlands
  6. 6 Pediatric Gastroenterology, Emma children's hospital amsterdam, Amsterdam, The Netherlands
  1. Correspondence to Kayleigh Vievermanns, Pediatrics, Catharina Hospital, Eindhoven 5623, The Netherlands; k.vievermanns{at}


Objective There is increasing evidence that probiotic supplementation in very preterm infants decreases the risk of necrotising enterocolitis (NEC), sepsis and mortality. The underlying mechanisms, including effects on the gut microbiota, are largely unknown. We aimed to systematically review the available literature on the effects of probiotic supplementation in very preterm infants on gut microbiota development.

Design A systematic review in Medline, Embase, Cochrane Library, CINAHL and Web of Science.

Setting Neonatal intensive care unit.

Patients Premature infants.

Intervention Probiotic supplementation.

Main outcome measures Gut microbiota.

Results A total of 1046 articles were screened, of which 29 were included. There was a large heterogeneity in study design, dose and type of probiotic strains, timepoints of sample collection and analysing techniques. Bifidobacteria and lactobacilli were the most used probiotic strains. The effects of probiotics on alpha diversity were conflicting; however, beta diversity was significantly different between probiotic-supplemented infants and controls in the vast majority of studies. In most studies, probiotic supplementation led to increased relative abundance of the supplemented strains and decreased abundance of genera such as Clostridium, Streptococcus, Klebsiella and Escherichia.

Conclusions Probiotic supplementation to preterm infants seems to increase the relative abundance of the supplemented strains with a concurrent decrease of potentially pathogenic species. These probiotic-induced microbial alterations may contribute to the decreased risk of health complications such as NEC. Future trials, including omics technologies to analyse both microbiota composition and function linked to health outcomes, are warranted to identify the optimal mixture and dosing of probiotic strains.

PROSPERO registration number CRD42023385204.

  • Neonatology
  • Intensive Care Units, Neonatal
  • Microbiology

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Contributors Conception and design: THD, NO, TGJdM. Acquisition of data, analysis and interpretation of data: KV, THD, NO. Drafting the article: KV. Revising the article critically for important intellectual content: THD, NO, FJ, HN, TGJdM. Guarantor: TGJdM. All the authors have read and approved the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.