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.

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

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

We will release deidentified metagenomic sequencing data from each participant to either database of Genotypes and Phenotypes (dbGaP) or Sequence Read Archive (SRA).

At the conclusion of the study

To be determined