GI Tract Biomarkers in Infants With Different Diets

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Obesity, Childhood

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 3 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breast Feeding<br>Infants who, when enrolled, are exclusively breast feeding. | |
| Formula Feeding<br>Infants who, when enrolled, are exclusively formula feeding. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolome | Metabolic products present in infant's feces | Enrollment | 
| Metabolome | Metabolic products present in infant's feces | 6 months | 
| Metabolome | Metabolic products present in infant's feces | 12 months | 
| Metabolome | Metabolic products present in infant's feces | 18 months | 
| Gut hormone gene expression | Transcriptional output of human epithelial cells in infant's feces | Enrollment | 
| Gut hormone gene expression | Transcriptional output of human epithelial cells in infant's feces | 6 months | 
| Gut hormone gene expression | Transcriptional output of human epithelial cells in infant's feces | 12 months | 
| Gut hormone gene expression | Transcriptional output of human epithelial cells in infant's feces | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone, Microbiome, Gut-brain axis, Satiety, Obesity, Metabolome