Safety, tolerability, and gastrointestinal effect of a Bifidobacterium-based synergistic synbiotic in infants and toddlers.

BACKGROUND

Bifidobacterium are critical components of the infant gut microbiome, yet most infants in developed countries are deficient.

METHODS

The ARTEMIS trial is the first clinical study in the United States to evaluate a synergistic synbiotic supplement in infants. It enrolled 114 participants in a randomized, double-blind, placebo-controlled study conducted to evaluate the safety, tolerability, and gastrointestinal colonization of the supplement in infants (n = 58) and toddlers (n = 56). The synbiotic contains four proprietary strains of Bifidobacterium, four complementary human milk oligosaccharides and vitamin D.

RESULTS

Safety and tolerability were assessed, with no statistically significant differences in adverse events or gastrointestinal symptom burden relative to placebo. The administered Bifidobacterium strains were significantly more prevalent and abundant in the synbiotic group. After four weeks of dosing, at least one administered strain was detected in 72% of infants (2-12 months) and 67% of toddlers (12-24 months). Synbiotic supplementation was associated with a significant increase in Bifidobacterium infantis abundance at the species level and human milk oligosaccharide utilization genes. Strains persisted through the two-week washout period, supporting intestinal colonization beyond active supplementation unlike other transient probiotics like Lactobacillus.

CONCLUSIONS

This synbiotic was safe, well tolerated, and achieved sustained Bifidobacterium colonization in infants and toddlers.

IMPACT: The ARTEMIS trial is the first U.S. clinical study to evaluate a synergistic synbiotic in infants combining multiple Bifidobacterium strains with human milk oligosaccharides (HMOs). Safety and tolerability were evaluated in infants and toddlers, with no statistically significant differences in adverse events or gastrointestinal tolerance compared with placebo. Infants and toddlers receiving the synbiotic showed significantly greater prevalence and abundance of the administered strains, demonstrating successful gut colonization and shifts in overall Bifidobacterium populations, along with increased abundance of HMO-utilization genes. In toddlers, synbiotic supplementation was associated with a significant improvement in sleep relative to placebo.