Safety and efficacy of a probiotic-containing infant formula supplemented with 2’-fucosyllactose: a double-blind randomized controlled trial

Design: double-blind randomized controlled trial in healthy term infants enrolled at <=14 days of age; n=289 formula-fed infants randomized to the two formulas; a non-randomized breastfed reference group (n=60) included for comparison.

Two regimens of a bovine milk-based starter infant formula: one containing L. reuteri DSM 17938 at 1×10^7 CFU/g; the other containing the same probiotic plus 2'-fucosyllactose (2'-FL) at 1.0 g/L; duration from enrollment (<=14 days old) to 6 months of age; exclusively fed the assigned formula for at least 4 months, after which complementary foods were introduced.

Weight gain from baseline to 4 months was non-inferior for the 2'-FL plus L. reuteri formula vs the L. reuteri-only formula (mean difference 0.26 g/day; 95% CI −1.26 to 1.79; lower CI > −3 g/day). Anthropometric z-scores, GI tolerance, stooling, and adverse events were similar between formula groups. Gut microbiota differed between regimens, with the 2'-FL group showing shifts toward a breastfed-like profile (e.g., lower Clostridioides difficile counts at 1 month; Bifidobacterium abundance closer to breastfed infants; BF infants had distinct gut biomarkers). Conclusion: 2’-FL added to L. reuteri-containing formula supports age-appropriate growth, is well tolerated, and may help shift gut microbiota toward that observed in breastfed infants.

High dropout rates in formula groups (EG 30%, CG 39%) and in BF group (41%), potentially reducing power for secondary outcomes; L. reuteri was present in the control formula, potentially limiting detection of incremental 2'-FL effects; strict 80% compliance criterion for per-protocol analysis reduced sample size; non-randomized breastfed reference group; healthy term infants only, limiting generalizability to preterm or ill infants.