A Synbiotic Infant Formula Promotes Balanced Immune-Microbiome Interactions in Term Infants: A Randomized Controlled Trial

Formula-fed infants have altered gut microbiota and immune development relative to breastfed infants. Human milk oligosaccharides (HMOs) and microbes able to ferment these, like Bifidobacterium infantis, promote healthy immune-microbiome interactions in breastfed infants. In this randomized trial, 240 healthy term infants in the Philippines received a synbiotic formula (SynF; seven HMOs, bovine milk oligosaccharides, and B. infantis LMG11588) or control formula (CtrlF) for 6 months. SynF supported growth non-inferior to CtrlF and near universal B. infantis colonization ( vs <10% in CtrlF). Markers of intestinal inflammation were lower in children fed SynF while secretory IgA was higher. SynF fed infants showed lower markers of systemic inflammation in plasma, slower immune cell maturation, and fewer upper respiratory tract infections (URTI) during their first 6 months of life. These findings suggest that synbiotic formula can dampen inflammatory responses to colonizing microbes and mild infections in fully formula-fed, term infants. Trial registration: NCT06073652 .