Clinical trial NCT03751137: GI Tract Biomarkers in Infants With Different Diets
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity, Childhood
Keywords: Microbiome
Gut-brain axis
Satiety
Hormone
Obesity
Metabolome
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
Collaborators: name: University of Delaware
First posted: 2018-11-23
Enrollment: 34
Sex: ALL
Minimum age (years): 6
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
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.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Microbiome
timeFrame: Enrollment
measure: Microbiome
timeFrame: 6 months
measure: Microbiome
timeFrame: 12 months
measure: Microbiome
timeFrame: 18 months
Secondary outcomes:
measure: Metabolome
timeFrame: Enrollment
measure: Metabolome
timeFrame: 6 months
measure: Metabolome
timeFrame: 12 months
measure: Metabolome
timeFrame: 18 months
measure: Gut hormone gene expression
timeFrame: Enrollment
measure: Gut hormone gene expression
timeFrame: 6 months
measure: Gut hormone gene expression
timeFrame: 12 months
measure: Gut hormone gene expression
timeFrame: 18 months
Other outcomes:
Locations:
city: Wilmington
country: United States
facility: Nemours Children's Hospital - Delaware
state: Delaware
Study officials:
affiliation: Nemours
name: Matthew Di Guglielmo, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: 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.