Probiotic Interventions for Preventing Necrotizing Enterocolitis in Preterm Infants

Necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality among preterm infants, characterised by inflammation, bacterial translocation and intestinal necrosis. The underdeveloped gut barrier, immature immune system and early-life antibiotic exposure conspire to disrupt microbial succession, creating a niche for pathogenic overgrowth. Probiotic interventions aim to restore microbial equilibrium by administering live beneficial microorganisms—most commonly strains of Bifidobacterium and Lactobacillus—during the critical early weeks of life. Clinical trials and meta-analyses consistently report reductions in NEC incidence, all-cause mortality and late-onset sepsis, especially when multispecies formulations are employed. Mechanistic studies reveal that probiotics enhance mucosal barrier function, modulate local and systemic immune responses, reduce gut pH through short-chain fatty acid production and compete with pathobionts for adhesion sites. Evidence also points to strain-specific effects on microbial community structure, metabolic output and host gene expression. Despite heterogeneity in dosing regimens, product quality and population characteristics, a growing consensus supports the routine use of selected probiotic combinations alongside breast milk feeding to mitigate NEC risk in very low birth weight and extremely preterm infants worldwide.

Research from Nature Portfolio

Recent studies employing high-resolution metagenomic and metabolomic analyses have shed light on how specific probiotic strains shape the preterm gut ecosystem. Longitudinal profiling of stool samples from very preterm infants revealed that supplementation with distinct combinations of Bifidobacterium bifidum, B. longum subsp. infantis and Lactobacillus acidophilus drives the transition into discrete preterm gut community types (PGCTs). Each PGCT is dominated by a characteristic Bifidobacterium species and correlates with postnatal age, antibiotic exposure and diet. Functional interrogation of faecal metabolites demonstrated associations between PGCTs and differential production of key compounds, such as acetate and lactate, which in turn influence intestinal epithelial gene expression in organoid models. These findings emphasise the importance of strain-specific formulations, showing that seemingly similar products can have markedly different impacts on microbiome assembly, metabolic function and host–microbe crosstalk in the immature gut.

Probiotic Interventions for Preventing Necrotizing Enterocolitis in Preterm Infants publication trend

The graph below shows the total number of articles in probiotic interventions for preventing necrotizing enterocolitis in preterm infants across all publications each year (not limited to Nature Index journals).

Technical terms

Necrotizing enterocolitis (NEC): A severe intestinal disease of preterm infants characterised by mucosal injury, inflammation and necrosis.

Preterm gut community type (PGCT): A classification of gut microbiome states in preterm infants, each dominated by specific bacterial taxa following probiotic supplementation.

Alpha-diversity: A measure of microbial richness and evenness within a single sample, often reflecting ecosystem stability.

Probiotic: A live microorganism which, when administered in adequate amounts, confers a health benefit on the host by modulating the gut microbiota and immune responses.

References

1. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis. PLOS ONE (2017).
2. Probiotics Prevent Late-Onset Sepsis in Human Milk-Fed, Very Low Birth Weight Preterm Infants: Systematic Review and Meta-Analysis. Nutrients (2017).
3. Bifidobacterium: Host–Microbiome Interaction and Mechanism of Action in Preventing Common Gut-Microbiota-Associated Complications in Preterm Infants: A Narrative Review. Nutrients (2023).
4. Strain-specific impacts of probiotics are a significant driver of gut microbiome development in very preterm infants. Nature Microbiology (2022).
5. Microbiota Supplementation with Bifidobacterium and Lactobacillus Modifies the Preterm Infant Gut Microbiota and Metabolome: An Observational Study. Cell Reports Medicine (2020).
6. Effects of Probiotics on Preterm Infant Gut Microbiota Across Populations: A Systematic Review and Meta-Analysis. Advances in Nutrition (2024).
7. Probiotics to improve the gut microbiome in premature infants: are we there yet?. Gut Microbes (2023).