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
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.010 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".