ARTEMIS trial data show Bifidobacterium-HMO synbiotic is safe and colonizes the infant, toddler gut

Results from the largest US randomized trial of a synbiotic supplement in infants and toddlers show that a Bifidobacterium-human milk oligosaccharide (HMO) formulation was safe, well tolerated, and achieved measurable gut colonization, according to findings published in Pediatric Research.¹ The ARTEMIS trial (NCT06746285), sponsored by Persephone Biosciences, enrolled 114 participants—58 infants aged 2 to 12 months and 56 toddlers aged 12 to 24 months—in a decentralized, randomized, double-blind, placebo-controlled design.¹

“The publication of our ARTEMIS study represents another important milestone for Persephone and reflects our commitment to building microbiome interventions supported by rigorous clinical evidence,” said Stephanie Culler, PhD, CEO and cofounder of Persephone Biosciences. “Parents today face hundreds of probiotic options, yet relatively few have been evaluated in randomized clinical trials.”

ARTEMIS trial design and colonization outcomes in infants and toddlers

Participants received either the synbiotic or placebo for 4 weeks, followed by a 2-week washout, with stool collected at 4 timepoints.¹ The active product contained 4 proprietary Bifidobacterium strains—2 B infantis strains plus 1 B longum and 1 B breve strain—combined with 4 HMOs and vitamin D.¹ No statistically significant differences in adverse events or gastrointestinal symptom burden emerged between the synbiotic and placebo arms, based on parent-reported outcomes and the validated Gastrointestinal and Gastroesophageal Reflux (GIGER) scale.¹ After 4 weeks of supplementation, at least 1 administered strain was detected in 72% of infants and 67% of toddlers, and colonization by B infantis and B breve strains persisted through the washout period in infants, distinguishing the effect from more transient probiotics such as Lactobacillus.¹ Supplementation also increased B infantis abundance at the species level and expanded HMO-utilization gene content, consistent with the formulation's intended mechanism.¹ An exploratory analysis found a statistically significant improvement in toddler sleep quality with the synbiotic relative to placebo, though the authors caution this outcome was not rigorously assessed and warrants dedicated study.¹

Bifidobacterium deficiency and atopic disease risk in US infants

The trial builds on Persephone's earlier My Baby Biome study, a cross-sectional analysis of 412 US infants that found roughly one-quarter had no detectable Bifidobacterium and a majority showed deficient levels, a pattern linked to increased risk of allergic disease, eczema, and asthma by age 2.² Reduced early Bifidobacterium colonization has been associated in the literature with gut dysbiosis and greater susceptibility to immune-mediated conditions, a gap the ARTEMIS authors say is only sparsely addressed by rigorously controlled US pediatric trials of probiotic and synbiotic products.¹

Synbiotic mechanism and product background

Unlike single-strain probiotics, a synergistic synbiotic pairs specific bacterial strains with prebiotic substrates selectively metabolized by those strains—in this case, fucosylated, sialylated, and neutral HMOs designed to support the Bifidobacterium strains' full HMO-utilization gene repertoire.¹ The formulation was developed from findings in the My Baby Biome cohort and represents Persephone's third peer-reviewed publication in its infant microbiome research program, following papers in Cell Host & Microbe and Communications Biology.

Interpreting the colonization and safety signal

“This publication provides further peer-reviewed evidence that Persephone's synbiotic is both safe and biologically active in infants and toddlers,” said Richard Insel, MD, research professor of pediatrics at the University of Rochester School of Medicine & Dentistry and the company's chief medical advisor. Insel noted that randomized trials assessing both safety and microbiome outcomes remain uncommon in pediatric probiotic research. Tanya Altmann, MD, the company's chief pediatric advisor, said studies like ARTEMIS are intended to give pediatricians firmer evidence when counseling parents on probiotic selection.

Limitations and next steps for the synbiotic program

The authors identify a relatively small sample size, parent-reported outcome measures inherent to the decentralized design, and an exploratory (not primary) sleep endpoint as limitations.¹ Persephone said it plans additional studies examining whether early microbiome intervention affects allergic disease and immune development in children.

References

1. 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 August 12, 2026. doi:10.1038/s41390-026-05318-4

2. Jarman JB, Torres PJ, Stromberg S, et al. Bifidobacterium deficit in United States infants drives prevalent gut dysbiosis. Commun Biol. 2025;8:867. doi:10.1038/s42003-025-08274-7

3. ClinicalTrials.gov. Evaluating the impact of synbiotic supplementation on infants and toddlers (ARTEMIS). NCT06746285. Updated August 2026. Accessed September 8, 2026. https://clinicaltrials.gov/study/NCT06746285

4. Persephone Biosciences, Inc. Persephone Biosciences publishes largest U.S. clinical study of an infant synbiotic in Pediatric Research, expanding clinical evidence for its infant synbiotics. News release. GlobeNewswire. August 12, 2026. https://www.globenewswire.com/news-release/2026/08/12/3343508/0/en/persephone-biosciences-publishes-largest-u-s-clinical-study-of-an-infant-synbiotic-in-pediatric-research-expanding-clinical-evidence-for-its-infant-synbiotics.html