Evaluating the Impact of Synbiotic Supplementation on Infants and Toddlers

Description

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

Study Overview

Study Details

Study overview

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.

Artemis: Evaluating the Impact of Synbiotic Supplementation on Infants and Toddlers

Evaluating the Impact of Synbiotic Supplementation on Infants and Toddlers

Condition
Gastrointestinal Tolerance of Probiotics in Infants
Intervention / Treatment

-

Contacts and Locations

San Diego

Persephone Biosciences, San Diego, California, United States, 92121

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • 1. Evidence of personally signed and dated informed consent document indicating that the caregiver(s) have been informed of all pertinent aspects of the study
  • 2. Caregiver(s) meet the following criteria:
  • 1. 18 Years or Older
  • 2. Legal Guardian of the Infant
  • 3. Intending to cohabitate with the infant/toddler for the duration of the study
  • 4. Can be reached by phone and email for the duration of the study
  • 5. Reads, writes, and speaks English
  • 6. Be able to accurately answer all portions of the questionnaire
  • 7. Have access to a working freezer
  • 8. Intending to be primary caregiver and study responder for duration of study
  • 9. Willing to provide synbiotic either in a bottle or some other format to the infant if on a fully liquid diet
  • 3. The PI considers the Caregiver likely to adequately comply with the study protocol requirements based on demonstrated compliance with initial questionnaires and agreement to complete all diaries
  • 4. The infant or toddler enrolled is:
  • 1. Healthy (has not been diagnosed with any chronic health conditions by a pediatrician)
  • 2. Still using diapers (to facilitate sample collection), and expected to continue in diapers for the duration of the study
  • 1. Infants/toddlers who have a medical condition or history that could increase the risk associated with study participation or interfere with the interpretation of study results, including:
  • * Evidence of major congenital malformations (e.g., cleft palate, extremity malformation)
  • * Any history or suspicion of systemic or congenital infections (e.g., human immunodeficiency virus, cytomegalovirus, syphilis)
  • * Severe gastroesophageal reflux (throwing up or spitting up more than a teaspoon of milk \> 8 times daily)
  • * Chronic vomiting (projectile, bilious or bloody emesis)
  • * Other severe medical or laboratory abnormality (acute or chronic) which, in the judgment of the investigator, would make the toddler inappropriate for entry into the study
  • 2. Infants/toddlers who are presently receiving or have received within three months prior to enrollment the following:
  • * Probiotic supplements
  • * Antibiotics
  • * Medication(s) or supplement(s) which are known or suspected to affect the following:
  • 3. Infants/toddlers with HIV or hepatitis or lactose sensitivity
  • 4. Infants/toddlers exposed to or displaying symptoms of a disease within 1 month of enrollment, including:
  • * Exposure to COVID-19
  • * Hematochezia (blood in the stools)
  • * Diarrhea (watery stools that takes the shape of a container \> 5x daily)
  • * Fever (38.2 degrees)
  • * Any other symptom which, in the judgment of the investigator, would make the infant inappropriate for entry into the study
  • 5. Currently participating or having participated in another clinical trial since birth

Ages Eligible for Study

2 Months to 24 Months

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

Persephone Biosciences,

Study Record Dates

2025-12-31