Flourish: Exploring the Early Infant Gut Microbiome

Official title

Flourish Study: A Randomized, Three-Arm Longitudinal Clinical Study of Microbiome-Guided Interventions in Cesarean-Born Infants

Overview

The goal of this clinical trial is to learn whether microbiome analysis, education, and personalized recommendations can improve gut health and reduce early markers of immune-related conditions in infants aged 0-3 months delivered via Cesarean section. The study aims to determine whether these interventions can increase beneficial bacteria, decrease C-section-associated microbiome signatures, reduce opportunistic pathogens, and improve functional potential for HMO digestion and SCFA production. The study also seeks to assess whether improvements in microbiome composition are associated with a reduced prevalence of early atopic symptoms. Researchers will compare three groups: a full intervention arm that receives microbiome reports, coaching, personalized recommendations, and educational materials; a limited intervention arm that receives simplified reports and basic recommendations; and a control arm that receives no results until study completion. This design allows evaluation of both a comprehensive intervention and a more scalable, minimal-results model. Participants will: 1. Provide six microbiome stool samples over a 24-month period. 2. Provide additional small stool samples at two timepoints for exploratory metabolomic analysis. 3. Receive microbiome reports and guidance according to their assigned study arm. 4. Complete surveys on infant health history, symptoms, diet, and environmental exposures. 5. Participate in standardized eczema assessment(s) administered by a Nurse Practitioner and evaluated by a Pediatric Allergy Specialist if any symptoms are reported. This study seeks to demonstrate that targeted microbiome support can positively shift gut microbial development in C-section infants and may reduce risks linked to the early stages of the atopic march. Findings may inform scalable strategies for delivering microbiome-based support in early life and improve long-term health outcomes for this high-risk population.

Interventions

• Dietary supplement Tailored Recommendations
  Recommendations are tailored to the infant's microbiome composition, functional gene profiles (e.g., HMO digestion and SCFA production pathways), age, feeding method, and reported symptoms. Guidance may include evidence-based suggestions related to probiotic use, prebiotic intake, and age-appropriate nutritional strategies intended to support healthy gut microbiome development. All recommendations are educational in nature, optional, and provided for consideration by parents or caregivers. No s
• Behavioral Consult Call
  Participants assigned to the full intervention arm will receive scheduled consult calls with a trained microbiome specialist as part of the study intervention. These are conducted remotely and are designed to support participant understanding of microbiome reports, review educational content, and discuss microbiome-informed recommendations in the context of the infant's age, feeding practices, and reported symptoms. For participants in the full intervention arm, consult calls may include discus
• Behavioral Educational Email Series
  Participants assigned to the full intervention arm will receive a structured educational email series delivered longitudinally over the course of the study. The email series provides evidence-based education on early infant gut microbiome development and its relationship to immune and allergic health outcomes, with links to blog articles summarizing current peer-reviewed research. Topics include Cesarean delivery and microbiome seeding, breastfeeding and human milk oligosaccharides, formula sel

Primary outcome measures

• Microbiota Composition [Time frame: 24 months]
• C-Section-Associated Microbiome Signatures [Time frame: 24 months]
• Opportunistic and Potentially Pathogenic Microbial Abundance [Time frame: 24 months]
• Functional Microbiome Capacity [Time frame: 24 months]
• Eczema Incidence / Atopic Symptoms [Time frame: 24 months]

Secondary outcome measures (3)

• HMO Digestion Functional Capacity [Time frame: 24 months]
• SCFA Production Functional Capacity [Time frame: 24 months]
• Parent-Reported Infant Health Outcomes [Time frame: 24 months]

Eligibility criteria

Inclusion criteria

• Infants are qualified for this study if they are 0 to 3 months of age at time of enrollment.
• Infants must have been delivered via Cesarean delivery (C-section), either scheduled or emergent.
• Infants must have been at least 36 weeks gestation at time of delivery.
• Infants and their caregivers must reside in the United States with a US mailing address.

Exclusion criteria

• Infants can not have been given probiotic supplements in their life at recruitment. This includes probiotic powder or supplements or formula with probiotic addition or multivitamin with probiotic addition.
• Twin and multiple birth infants are not accepted in this study.
• Infants cannot have the following existing health conditions:
• Gastrointestinal conditions: Hirschsprung disease, eosinophilic gastrointestinal disorders (EGID) including eosinophilic esophagitis (EoE), necrotizing enterocolitis (NEC), short bowel syndrome (SBS)
• Immune or auto-immune conditions: Severe Combined Immunodeficiency (SCID), human immunodeficiency virus (HIV)), excluding eczema and rashes
• Congenital conditions: cleft lip or cleft palate, congenital heart disease, cerebral palsy, fragile X syndrome, down syndrome, spina bifida, cystic fibrosis, phenylketonuria (PKU), congenital hypothyroidism (CHT), galactosaemia)
• Blood disorders (sickle cell disease, thalassemia, hemophilia)
• Infant or any immediate family member has previously received results from an at-home microbiome stool test (excluding standard clinical diagnostic testing such as stool culture or pathogen testing)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

United States · 1 center

• Seeding Labs INC — Austin

Publications

• Shao Y, Forster SC, Tsaliki E, Vervier K, Strang A, Simpson N, Kumar N, Stares MD, Rodger A, Brocklehurst P, Field N, Lawley TD. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature. 2019 Oct;574(7776):117-121. doi: 10.1038/s41586-019-1560-1. Epub 2019 Sep 18. PMID 31534227
• Galazzo G, van Best N, Bervoets L, Dapaah IO, Savelkoul PH, Hornef MW; GI-MDH consortium; Lau S, Hamelmann E, Penders J. Development of the Microbiota and Associations With Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood. Gastroenterology. 2020 May;158(6):1584-1596. doi: 10.1053/j.gastro.2020.01.024. Epub 2020 Jan 1 PMID 31958431
• Nieto PA, Nakama C, Trachsel J, Goad D, Soderborg TK, Tan DS, Orlandi A, Yuan Q, Song E, Mueller NT, Mars RA, Hoy CS, Sukhum KV. Improving immune-related health outcomes post-cesarean birth with a gut microbiome-based program: A randomized controlled trial. Pediatr Allergy Immunol. 2025 Sep;36(9):e70182. doi: 10.1111/pai.70182. PMID 40898384

Identifiers

NCT: NCT07333482 · FLOURISH_14952

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗