GI Tract Biomarkers in Infants With Different Diets

Obesity, Childhood Clinical Trial

Official title:

Longitudinal, Prospective Comparison of the Gastrointestinal Tract of Breastfed and Formula Fed Infants Via Fecal Analysis of the Microbiome, Intestinal Epithelial Cell Expression of Gut Hormones, and Fecal Analysis of the Metabolome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03751137
• Other study ID #: 822736
• Status: Active, not recruiting
• Start date: March 10, 2016
• Est. completion date: June 30, 2026

Study information

• Verified date: September 2023
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Childhood obesity is increasing with more than one-third of adolescents currently overweight and one in five with obesity. The lifelong incidence of obesity-related morbidities is also increasing with childhood obesity. It is not yet known how obesity develops in an individual, specifically in early childhood. Further, it is unclear what mechanistic role a child's earliest nutrition or changing intestinal flora has in the etiology of obesity. Very young children are developing appetite and satiety patterns early in life. Nutrition and gut microbial flora have impact on how these processes unfold, but specific mechanisms are not yet well understood. The investigators hypothesize that formula-fed infants with changes in their microbial flora are more likely to have altered carbohydrate metabolism, evidenced by greater imbalances of fatty acid production, and are more likely to have accelerated growth trajectory due to satiety disruption. The investigators further hypothesize that altered carbohydrate metabolism, e.g. imbalances of short- and long-chain fatty acid levels in the gut, stimulate cellular stress and affect specific gut hormones. This study will compare the microbiome of the intestinal microbial flora in two groups of infants, one breast fed and the other formula fed, using longitudinally collected fecal samples from both groups. Samples will be subjected to shotgun metagenomic analysis and simultaneous metabolomic analysis. A bioinformatics approach will elucidate key differences among and between sample groups, and will further analyze bacterial gene expression levels related to carbohydrate metabolism. This study will compare the expression of human proteins involved in cellular stress response and gut peptide signaling by applying quantitative Reverse Transcriptase-Polymerase Chain Reaction to human messenger RNA isolated from the longitudinally collected samples from both groups. Finally, this study will monitor the trajectory of growth and feeding over the first 2 years of life. The project's focus on the influence of different early feeding types, microbial flora changes, and altered carbohydrate metabolism leading to disruption of gut-brain signaling will provide critical data for host:microbiome interactions and translational therapeutic targets.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: June 30, 2026
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 3 Months

Eligibility

Inclusion Criteria:

• Otherwise healthy, male or female term infants
• Exclusively breast or formula feeding
• Never been exposed to oral or intravenous antibiotics or probiotics

Exclusion Criteria:

• Maternal antibiotic use while breast-feeding
• Infant or maternal use of probiotics
• Current or recent (<14 days) gastrointestinal infection (viral, bacterial, or fungal)
• Gastrointestinal mucosal disease, or significant constipation
• Consuming formula that is not standard cow's milk formula
• Infants on acid suppression medications or infants receiving high-density formula (>20 calories/ounce) may be enrolled and will be analyzed separately

Related Conditions & MeSH terms

• Obesity, Childhood
• Pediatric Obesity

Locations

Country	Name	City	State
United States	Nemours Children's Hospital - Delaware	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Nemours Children's Clinic	University of Delaware

Country where clinical trial is conducted

United States, 

References & Publications (2)

Di Guglielmo MD, Franke K, Cox C, Crowgey EL. Whole genome metagenomic analysis of the gut microbiome of differently fed infants identifies differences in microbial composition and functional genes, including an absent CRISPR/Cas9 gene in the formula-fed — View Citation

Di Guglielmo MD, Franke KR, Robbins A, Crowgey EL. Impact of Early Feeding: Metagenomics Analysis of the Infant Gut Microbiome. Front Cell Infect Microbiol. 2022 Mar 4;12:816601. doi: 10.3389/fcimb.2022.816601. eCollection 2022. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Microbiome	Metagenomic analysis of microbial organisms in infant's feces	Enrollment
Primary	Microbiome	Metagenomic analysis of microbial organisms in infant's feces	6 months
Primary	Microbiome	Metagenomic analysis of microbial organisms in infant's feces	12 months
Primary	Microbiome	Metagenomic analysis of microbial organisms in infant's feces	18 months
Secondary	Metabolome	Metabolic products present in infant's feces	Enrollment
Secondary	Metabolome	Metabolic products present in infant's feces	6 months
Secondary	Metabolome	Metabolic products present in infant's feces	12 months
Secondary	Metabolome	Metabolic products present in infant's feces	18 months
Secondary	Gut hormone gene expression	Transcriptional output of human epithelial cells in infant's feces	Enrollment
Secondary	Gut hormone gene expression	Transcriptional output of human epithelial cells in infant's feces	6 months
Secondary	Gut hormone gene expression	Transcriptional output of human epithelial cells in infant's feces	12 months
Secondary	Gut hormone gene expression	Transcriptional output of human epithelial cells in infant's feces	18 months