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Evaluating the bifidogenic effect of various infant formula supplementations: a systematic review and network meta-analysis of randomized controlled trials
Published online by Cambridge University Press: 02 September 2025
Abstract
This study aimed to investigate the effects of infant formula supplements on Bifidobacterium level in the infant gut through a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs).
Systematic review included PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL to identify RCTs evaluating the effects of formulas supplemented with prebiotics, probiotics, synbiotics, β-palmitic acid, or combinations of β-palmitic acid with prebiotics on infant gut Bifidobacterium levels. A meta-analysis compared bifidogenic effects to standard formula. The main outcome was the relative abundance (RA) of Bifidobacterium in fecal samples measured by various microbiota assessment techniques, with effect sizes as mean differences and standard deviations. An overall effect estimate was derived using a random-effects model. NMA assessed formula effects using breastfeeding as the reference.
Nineteen studies were included. Compared to standard formula, supplementation with prebiotics (p < 0.0001), synbiotics (p < 0.0001), β-palmitic acid (p = 0.0005), or β-palmitic acid combined with prebiotics (p < 0.0001) significantly increased Bifidobacterium levels in the infant gut. Probiotic supplementation showed no significant effect (p = 0.9755). NMA and p-score ranking, comparing formulas to breastmilk, indicated that prebiotic-supplemented formulas with the lowest ranking p-score (0.2764), most closely resembled breastfeeding’s bifidogenic effect. However, prebiotics and probiotics were analyzed as broad categories, and group variability may affect outcomes. In conclusion, formula supplementation with prebiotics, synbiotics, β-palmitic acid, or combinations of β-palmitic acid with prebiotics increased the RA of Bifidobacterium in infant’s gut, with prebiotic formula most closely mimicking the bifidogenic effects of breastfeeding.
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- © The Author(s), 2025. Published by Cambridge University Press in association with The International Society for Developmental Origins of Health and Disease (DOHaD)
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Mansouri et al. supplementary material
Mansouri et al. supplementary material
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