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Risks and benefits of probiotics for preterm neonates: threshold of comfort or fear?

Pediatric Research (2025)Cite this article

A Correction to this article was published on 05 August 2025

The Original Article was published on 13 May 2025

This article has been updated

Necrotizing enterocolitis (NEC) is severe gastro-intestinal disease of preterm infants and has mortality rates of 15–25%.1,2,3 Treatment of NEC is mainly supportive. Approximately half of all infants with Bell stage II NEC respond to bowel rest, antibiotics, and supportive medical measures, but others develop progressive bowel disease and require surgical intervention and may result in long-term morbidity including short bowel syndrome and neurodevelopmental impairment.1,3,4,5,6 Except for the receipt of human milk and antenatal steroids, no intervention has shown to have a clear benefit in preventing NEC.7,8,9 With NEC incidence rate between 5 and 12% in very low birth weight (VLBW) infants and a high risk of mortality and morbidity, there is a clear need for effective and safe preventive therapies.10

Despite decades of research, the etiopathogenesis of NEC is unclear. Immaturity of the gut mucosal barrier, mucosal injury, ischemia, inflammation, and microbial dysbiosis are all considered plausible etiopathogenic factors in this multi-factorial disease. Microbial dysbiosis preceding NEC is characterized by a Proteobacterial bloom and decrease in other phyla namely Firmicutes and Bacteroidetes.11 Altered microbial development and growth may eventually allow luminal bacteria to translocate into the bowel wall that lead to dysregulated inflammation and intestinal necrosis. Microbiome optimization to offset dysbiosis is conceptually promising in the prevention of NEC. Microbiome optimizing strategies include administering targeted antibiotics, enteral supplementation of specific strains of beneficial bacteria (probiotics), administration of microbial products and para-probiotics (inactivated probiotics), fecal transplantation, or by modulating the TLR4 response to dysbiosis.8,12

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Change history

  • 04 August 2025

    The original online version of this article was revised: In this article ref. 25 was missing and should have been 'Feldman K. et al. Incidence of probiotic sepsis and morbidity risk in premature infants: a meta-analysis. Pediatr Res. https://doi.org/10.1038/s41390-025-04072-3 (2025). Epub ahead of print.'.

  • 05 August 2025

    A Correction to this paper has been published: https://doi.org/10.1038/s41390-025-04339-9

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Acknowledgements

M.P. received funding from NIH (R01HD112886) and P.S. has received funding from the Canadian Institutes of Health Research (APR-126340 and PBN 150642).

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  1. Department of Pediatrics, Division of Neonatology, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, USA

    Mohan Pammi

  2. Department of Pediatrics, Mount Sinai Hospital, Toronto and University of Toronto, Toronto, ON, Canada

    Prakesh S. Shah

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Correspondence to Mohan Pammi.

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The original online version of this article was revised: In this article ref. 25 was missing and should have been 'Feldman K. et al. Incidence of probiotic sepsis and morbidity risk in premature infants: a meta-analysis. Pediatr Res. https://doi.org/10.1038/s41390-025-04072-3 (2025). Epub ahead of print.'.

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Pammi, M., Shah, P.S. Risks and benefits of probiotics for preterm neonates: threshold of comfort or fear?. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04267-8

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