GI Tract Biomarkers in Infants With Different Diets

NCT03751137 | Completed

• 1 other identifier: 822736
• Study Type: observational
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity, Childhood

Keywords

Microbiome; Gut-brain axis; Satiety; Hormone; Obesity; Metabolome

Outcome Measures

Primary Outcomes (4)

• Microbiome

  Metagenomic analysis of microbial organisms in infant's feces

  Enrollment

• Microbiome

  Metagenomic analysis of microbial organisms in infant's feces

  6 months

• Microbiome

  Metagenomic analysis of microbial organisms in infant's feces

  12 months

• Microbiome

  Metagenomic analysis of microbial organisms in infant's feces

  18 months

Secondary Outcomes (8)

• Metabolome

  Enrollment

• Metabolome

  6 months

• Metabolome

  12 months

• Metabolome

  18 months

• Gut hormone gene expression

  Enrollment

Study Arms (2)

Breast Feeding

Infants who, when enrolled, are exclusively breast feeding.

Formula Feeding

Infants who, when enrolled, are exclusively formula feeding.

Eligibility Criteria

• Age: 6 Weeks - 3 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Infants who are either exclusively breast feeding or exclusively formula feeding are eligible to enroll if meeting other criteria.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nemours Children's Clinic: lead
• University of Delaware: collaborator

Study Sites (1)

Nemours Children's Hospital - Delaware

Wilmington, Delaware, 19803, United States

Location

Related Publications (2)

• 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.

  PMID: 35310842 BACKGROUND

• 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 cohort. Hum Microb J. 2019 Jun;12:100057. doi: 10.1016/j.humic.2019.100057. Epub 2019 May 25.

  PMID: 34278055 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Fecal samples containing microbial genetic material and, to a lesser degree, human intestinal epithelial cells with human genetic material.

MeSH Terms

Conditions

Pediatric Obesity; Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Matthew Di Guglielmo, MD PhD

  Nemours

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Division of General Academic Pediatrics

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 23, 2018
• Study Start: March 10, 2016
• Primary Completion: July 31, 2021
• Study Completion: May 30, 2025
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ANALYTIC CODE
• Time Frame: At the conclusion of the study
• Access Criteria: To be determined

Locations

US (1)