Evaluating the Impact of Synbiotic Supplementation on Infants and Toddlers

Summary

Background and Significance:

Bifidobacterium longum subspecies infantis (B. infantis) and other infant associated Bifidobacterium (such as Bifidobacterium longum subspecies longum and Bifidobacterium breve) are known to be important bacteria in the infant gut microbiome. A lack of Bifidobacterium in the infant gut may lead to disordered development of the infant microbiome and immune system, which can contribute to the development of gastrointestinal issues, pathogenic infections, and immune-related conditions including allergic disease and autoimmune disorders. The investigators hypothesize that establishing Bifidobacterium in the infant gut through delivery of a synbiotic, containing bifidobacterium and human milk oligosaccharides (HMOs; Bifidobacterium's primary nutrient source) may modulate the microbiome and correct this disruption.

Research Question:

Does synbiotic supplementation on infants and toddlers of various ages alter the gut microbiome as measured by GI-tolerance, fecal microbiome composition, and fecal metabolic profile?

Objectives:

* Demonstrate shifts in microbiome composition and metabolism
* Demonstrate tolerance by observing neutral or positive shifts in GI related behaviors

Study Design Overview:

Participants Infants aged 2-24 months will be enrolled to evaluate the ability of a synbiotic (human milk oligosaccharide + a Bifidobacterium blend (B. infantis, B. longum, and B. breve)) to modulate the gut microbiome. Infants will be randomly split into two cohorts, one that receives synbiotic supplementation and one that receives a placebo control (lactose).

Initially, only ages 12-24 months will be enrolled (first 25 participants), and a safety review will be performed prior to enrolling younger infants.

Cohorts

* Cohort 1 (supplementation) participants will be aged 2 months to 24 months. They will receive synbiotic supplementation for 1 month.
* Cohort 2 (no supplementation) participants will be aged 2 months to 24 months. Will receive placebo (lactose) over the course of 1 month.

Design Caretakers will be recruited and screened using an online questionnaire to determine eligibility and cohort assignment. They will give consent using an online one-party consent form (Appendix 1). Participants will be distributed randomly between cohorts 1 and 2. Participants will be shipped the synbiotic or placebo (lactose) and a set of stool sampling kits. Calls with the participant will take place throughout the study as necessary to explain participant responsibilities and ensure compliance. Two sample types will be collected during the study, a full fecal sample and a DNA/RNA tube only. The full fecal sample will be collected at the beginning and end of supplementation and the DNA/RNA tube only will be collected at all other time points. Samples will be collected at supplementation start, one week after supplementation, four weeks after supplementation start (coinciding with the end of supplementation) and 6 weeks after supplementation start (coinciding with a 2 week washout period). Journals and questionnaires will be used for the duration of supplementation as well as 2 weeks before and after to assess the impact of supplementation.

Laboratory Assessments:

Stool samples will be obtained for each subject. The first sample will be taken before supplementation start. Additional samples will be collected: after 1 week of supplementation, after 1 month of supplementation, and after a 2 week period of no supplementation (a washout period). All samples will be collected at home and shipped back to Persephone Biosciences for processing. The initial sample and the sample after 4 weeks of supplementation will be full samples for metagenomic, metabolomic, and proteomic analysis. The 1 week after supplementation and 2 week post supplementation samples will be DNA/RNA tube samples for metagenomics only. Microbial whole genome sequencing, metabolite analysis, and immune profiling will be performed on stool from complete stool kits. Microbial whole genome sequencing alone will be performed on the DNA/RNA tube kits.

Data Collection:

Demographic data, general health information, diet and lifestyle information will be collected from the subjects (all self-reported). Journals and questionnaires will be used to evaluate the impact of the synbiotic.

Conditions

• Gastrointestinal Tolerance of Probiotics in Infants

Interventions

DIETARY_SUPPLEMENT

Synbiotic Supplement

Participants will be given 1g of a synbiotic product each day, containing 4 microbial strains isolated from an infant gut (total of 1 billion cfu) and a mixture of 4 human milk oligosaccharides. Parents will administer the product by dissolving in breast milk, formula, or water, or mixing with food.

DIETARY_SUPPLEMENT

Lactose (inactive placebo)

Participants will be given 1g of lactose as a placebo. Parents will administer the product by dissolving in breast milk, formula, or water, or mixing with food.

Sponsors & Collaborators

• Persephone Biosciences

  lead INDUSTRY

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

2 Months

Max Age

24 Months

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2025-01-01

Primary Completion

2025-09-30

Completion

2025-12-31

Countries

• United States

Study Locations