Probiotic supplementation – does it prevent or cause neonatal sepsis? Original paper

What was reviewed?

This paper is a narrative review that examined whether probiotic supplementation in preterm infants prevents late-onset neonatal sepsis or, conversely, introduces new risks of probiotic-associated infection. The authors synthesized evidence from randomized controlled trials, systematic reviews, meta-analyses, and large observational cohorts to clarify the relationship between probiotics, late-onset sepsis, necrotizing enterocolitis, mortality, and safety. Rather than testing a single intervention, the review critically evaluated accumulated clinical and mechanistic evidence to resolve ongoing controversy in neonatal practice regarding routine probiotic use in intensive care settings.

Who was reviewed?

The review focused on preterm and very low birthweight infants cared for in neonatal intensive care units, including extremely low birthweight infants who carry the highest risk of necrotizing enterocolitis, bloodstream infection, and mortality. The populations reviewed spanned high-income and low- to middle-income settings, reflecting differences in baseline sepsis risk, feeding practices, antimicrobial exposure, and infection control. Clinicians, therefore, should interpret the findings in the context of gestational age, feeding with human milk, and local NICU practices.

What were the most important findings?

Across more than 50 randomized trials and multiple meta-analyses, probiotic supplementation consistently reduced necrotizing enterocolitis and all-cause mortality in preterm infants, establishing probiotics as one of the most effective interventions in neonatology. In contrast, the effect on late-onset sepsis was modest or absent, with pooled estimates suggesting little to no clinically meaningful reduction. Mechanistically, probiotics modulate the gut microbiome by increasing beneficial taxa such as Bifidobacterium and Lactobacillus, improving epithelial barrier integrity, enhancing secretory IgA, and competitively excluding potential pathogens such as coagulase-negative staphylococci and Staphylococcus aureus. These microbiome shifts may reduce pathogen density and translocation, but the translation into lower bloodstream infection rates appears inconsistent and strain dependent. Importantly, probiotic-associated sepsis was rare, generally occurring in less than 0.5% of exposed infants, often in the setting of severe gut pathology such as necrotizing enterocolitis or focal intestinal perforation. Evidence on antimicrobial resistance suggested no clear increase in resistance burden and, in some studies, a reduction in resistance gene abundance, although data remain limited.

What are the greatest implications of this review?

For clinicians, the central implication is that probiotics offer a favorable benefit–risk profile for preventing necrotizing enterocolitis and reducing mortality, even if their role in preventing late-onset sepsis is limited. Decisions should emphasize product quality, strain specificity, infection control practices, and careful handling in vulnerable infants with compromised gut integrity. The review reinforces that probiotics should be viewed as microbiome-modulating therapies with broad systemic effects rather than as direct anti-sepsis agents.