Bifidobacterium-based synbiotic shows safety and gut colonization in infants and toddlers

A synbiotic containing multiple Bifidobacterium strains and human milk oligosaccharides (HMOs) was well tolerated and resulted in intestinal colonization in infants and toddlers, according to findings from the randomized ARTEMIS trial published in Pediatric Research.

The study enrolled 114 children, including 58 infants aged 2 to 12 months and 56 toddlers aged 12 to 24 months. Investigators described ARTEMIS as the first US clinical study to evaluate a synergistic synbiotic in infants that combines multiple Bifidobacterium strains with HMOs.

The supplement contained 4 Bifidobacterium strains—2 Bifidobacterium longum subsp infantis strains, 1 B longum strain, and 1 Bifidobacterium breve strain—along with 4 HMOs and vitamin D. The primary outcomes were safety and tolerability, with intestinal colonization and microbiome changes evaluated as secondary outcomes.

How was safety and tolerability assessed?

Participants were randomly assigned to receive the synbiotic or placebo for 4 weeks, followed by a 2-week washout period. Thirty-two infants received the synbiotic, and 26 received placebo; among toddlers, 31 received the synbiotic and 25 received placebo. Forty-seven infants and 44 toddlers completed the study.

Investigators found no significant difference in treatment-emergent adverse events between the groups, and no serious adverse events were reported. Gastrointestinal events were the most common, followed by skin events.

“The data suggest that the synbiotic study product was well-tolerated in this pediatric population,” the investigators wrote. “Most AEs were mild, self-limited, and consistent with expected background pediatric illnesses.”

Tolerability was assessed using the caregiver-reported Gastrointestinal and Gastroesophageal Reflux Scale and observational diaries. No significant differences between the synbiotic and placebo groups were observed in gastrointestinal symptom scores, stooling, gas, or general gastrointestinal distress.

An exploratory analysis identified improved sleep quality among toddlers receiving the synbiotic compared with placebo; however, the investigators cautioned that the study was not designed to rigorously evaluate sleep.

Did the synbiotic alter the gut microbiome?

Colonization analyses showed that among participants without the administered strains at baseline, at least 1 synbiotic strain was detected during supplementation in 72% of infants and 67% of toddlers. Supplementation was also associated with increased abundance of B infantis at the species level.

At the strain level, investigators observed colonization of both administered B infantis strains and the B breve strain in infants and toddlers. In infants, colonization persisted after supplementation ended. The administered B longum strain did not demonstrate a statistically significant increase, which investigators noted could be related to its relatively high baseline abundance.

The researchers also observed increases in genes involved in HMO utilization, consistent with the increase in B infantis. However, supplementation did not produce statistically significant changes in overall Bifidobacterium abundance at the genus level.

What should pediatricians consider?

The findings primarily establish short-term safety, tolerability, and microbiome effects rather than clinical benefits associated with supplementation. The authors noted that additional studies are needed to determine whether the observed microbiome changes translate into measurable health outcomes.

“Limitations of this work include the relatively small sample size and the reliance on parent reporting as a consequence of the decentralized study design,” the investigators wrote. They added that probiotics and synbiotics require “more rigorous clinical trials, combining rigorous clinical standards with detailed evaluation of the microbiome, to understand impact and mechanism of action.”

Reference

Jarman JB, Torres PJ, Baum C, et al. Safety, tolerability, and gastrointestinal effect of a Bifidobacterium-based synergistic synbiotic in infants and toddlers. Pediatr Res. Published online 2026. doi:10.1038/s41390-026-05318-4.