Effects of Infant Formula Supplemented With Prebiotics on the Gut Microbiome, Gut Environment, Growth Parameters, and Safety and Tolerance: A Systematic Review and Meta-Analysis.

CONTEXT

Prebiotics are often added to infant formulas to mimic the benefits of oligosaccharides found in human milk.

OBJECTIVE

This systematic review and meta-analysis evaluated the effects of prebiotic-supplemented cow's milk-based formula on the gut microbiota, gut environment, growth parameters, and safety and tolerance in infants ≤6 months old, compared with a standard formula or human milk comparator.

DATA SOURCES

Searches were performed in the PubMed, Embase, Cochrane Central Register of Controlled Trials, and ProQuest Dissertations & Theses databases. Articles were included that reported on randomized controlled trials, were published from inception until April 2024, and met prespecified inclusion and exclusion criteria.

DATA EXTRACTION

Outcomes included gut microbiota (eg, diversity; taxa at phylum, family, genus and species levels), gut environment (eg, pH, secretory immunoglobulin A, fecal calprotectin, fecal metabolites), growth parameters (eg, z scores), and safety and tolerance. Fixed or random effects models were used and mean differences (MDs) with 95% CIs were calculated to assess pooled effects. Risk of bias was assessed using the Cochrane Collaboration Tool (RoB 2).

DATA ANALYSIS

A total of 30 articles met inclusion criteria, with 5290 infants included. Whereas effects on Lactobacillus were inconsistent, prebiotic formula supplementation increased Bifidobacterium counts (k = 7 [MD: 0.49; 95% CI, 0.27-0.71]; I2 = 13%; P < .00001) and decreased fecal pH (k = 7 [MD: -0.39; 95% CI, -0.57 to -0.20]; I2 = 0%; P < .0001) compared with standard formula. Prebiotic formula supplementation increased total bacteria compared with human milk (MD: 0.41 [95% CI, 0.17-0.65]; I2 = 8%; P = .0006). In terms of growth parameters, weight-for-age z scores favored the prebiotic formula group compared with the human milk group (k = 2 [MD: 0.23; 95% CI, 0.04-0.42]; I2 = 7%; P = .02).

CONCLUSIONS

Prebiotic supplementation in infant formula can positively alter the gut microbiota, particularly Bifidobacterium, without negative impacts on growth. Standardized, high-quality research is needed to confirm the study findings and inform guidelines for prebiotic use in infant nutrition.

SYSTEMATIC REVIEW REGISTRATION

PROSPERO registration no. CRD42021253589.