Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome.

Early-life colonization of the intestinal tract is a dynamic process influenced by numerous factors. The impact of probiotic-supplemented infant formula on the composition and function of the infant gut microbiota is not well defined. We sought to determine the effects of a bifidobacteria-containing formula on the healthy human intestinal microbiome during the first year of life. A double-blind, randomized, placebo-controlled study of newborn infants assigned to a standard whey-based formula containing a total of 10 colony-forming units (CFU)/g of , , , subspecies (intervention), or to a control formula without bifidobacteria (placebo). Breastfed controls were included. Diversity and composition of fecal microbiota were determined by 16S ribosomal RNA gene amplicon sequencing, and metabolite profiles were analyzed by ultrahigh-performance liquid chromatography-mass spectrometry over a period of 2 y. Infants ( = 106) were randomly assigned to either the interventional ( = 48) or placebo ( = 49) group; 9 infants were exclusively breastfed throughout the entire intervention period of 12 mo. Infants exposed to bifidobacteria-supplemented formula showed decreased occurrence of and spp. associated with changes in lipids and unknown metabolites at month 1. Microbiota and metabolite profiles of intervention and placebo groups converged during the study period, and long-term colonization (24 mo) of the supplemented strains was not detected. Significant differences in microbiota and metabolites were detected between infants fed breast milk and those fed formula ( < 0.005) and between infants birthed vaginally and those birthed by cesarean delivery ( < 0.005). No significant differences were observed between infant feeding groups regarding growth, antibiotic uptake, or other health variables ( > 0.05). The supplementation of bifidobacteria to infant diet can modulate the occurrence of specific bacteria and metabolites during early life with no detectable long-term effects. This trial was registered at germanctr.de as DRKS00003660.