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Updated: Jul 18, 2026

A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
Probiotic supplementation - does it prevent or cause neonatal sepsis?
Nicholas D Embleton1, Chris H P van den Akker2, Belal N Alshaikh3
1Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; Newcastle University, Newcastle upon Tyne, UK.
Insights
Probiotic supplementation significantly reduces necrotizing enterocolitis (NEC) and mortality in preterm infants. While effects on late-onset sepsis (LOS) are modest, the overall safety and benefits support their use in neonatology.
Area of Science:
- Neonatal Medicine
- Microbiome Research
- Clinical Nutrition
Background:
- Probiotic supplementation is widely studied in preterm infants.
- Over 50 randomized controlled trials exist for probiotics in neonatology.
- Established benefits include reduced necrotizing enterocolitis (NEC) and mortality.
Purpose of the Study:
- To examine the relationship between probiotic use and late-onset sepsis (LOS) in preterm infants.
- To review mechanistic pathways, clinical evidence, and safety data.
- To assess the overall benefit-risk profile of probiotics for preterm infants.
Main Methods:
- Systematic reviews and meta-analyses of randomized controlled trials.
- Analysis of mechanistic pathways for sepsis reduction.
- Evaluation of safety data, including adverse events and probiotic-induced sepsis.
- Assessment of evidence for NEC and mortality reduction.
Main Results:
- Probiotics show a modest effect on reducing LOS (RR 0.89, low certainty).
- Mechanisms include pathogen exclusion, enhanced barrier function, and improved immunity.
- Serious adverse events are rare; probiotic-induced sepsis is <0.5% risk.
- Robust evidence supports significant reduction in NEC and all-cause mortality.
Conclusions:
- Probiotics are highly beneficial for preterm infants, primarily for NEC and mortality reduction.
- The impact on LOS is currently considered modest with low certainty.
- The overall benefit-risk profile strongly favors probiotic use despite ongoing research needs for LOS and resistome impacts.
Abstract:
Probiotic supplementation in preterm infants is one of the most extensively studied interventions in neonatal medicine, with over 50 randomised controlled trials. This paper examines the relationship between probiotic supplementation and late onset sepsis (LOS), considering mechanistic pathways, clinical evidence, and safety profile. Multiple systematic reviews and meta-analyses consistently show that probiotics reduce necrotising enterocolitis (NEC) incidence and all-cause mortality in preterm infants, establishing them as one of the most beneficial interventions in neonatology. Current evidence suggests modest effects on LOS, with Cochrane systematic reviews reporting relative risk 0.89 (95 % CI 0.82-0.97) but with low certainty. Mechanisms supporting LOS reduction include competitive pathogen exclusion, enhanced epithelial barrier function, improved immune responses, and reduced time to full enteral feeding with decreased intravenous access requirements. The safety profile of probiotics is reassuring, with serious adverse events being exceptionally rare. Probiotic-induced sepsis probably occurs in less than 0.5 % of treated infants, representing a very low risk that must be weighed against the likely substantial benefits for NEC and mortality reduction. Product contamination and other quality issues exist but appear manageable with appropriate quality control. Given the robust evidence for NEC and mortality reduction, probiotics represent a valuable intervention for preterm infants but may have limited, if any impact on sepsis. While their specific role in LOS prevention and impacts on the resistome requires further investigation, the overall benefit-risk profile strongly favors their use. Future research will further refine understanding of optimal strain selection and implementation strategies for maximizing clinical benefits while maintaining safety.
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