DESCRIPTION (provided by applicant): Obesity is a significant national health problem that spares no age group. Approximately 10 percent of children less than two years of age in the U.S. have weight-for-length above the 95th percentile. Childhood obesity is particularly concerning for African American children. By ages 2 to 5 years, 19 percent of African American children are obese (BMI>95th percentile). Rapid weight gain in the first 4 to 6 months of life is associated with obesity later in childhood, so infancy may be a critical window for obesity prevention. This age range has other advantages for future prevention measures because of frequent contact with health care providers, parental control over infant diet, and the possibility that metabolic programming may occur in this developmental window. However, to develop public health strategies to prevent rapid weight gain in infancy, the causal factors must be well understood. Maternal BMI, gestational weight gain, birth delivery mode, antibiotic exposure, pattern of infant weight gain, feeding practices, maternal stress, socioeconomic status, population ancestry and genetic predisposition have been associated with childhood obesity risk, but their mechanisms of action, synergy, and relative importance remain unclear. Recent studies in animal models demonstrate cause-and-effect relationships between gut bacteria, their metabolites, and obesity development. In children and adults, alteration of gut microbiota is associated with obesity, and indirect effects of microbiota on appetite regulation have been implicated. Changes in gut microbiota in the first 2 years of life have been documented. A major knowledge gap is the link between changes in gut microbiota and its metabolome and excess weight gain during this young age. This is a prospective longitudinal study of children ages birth to 24 months. We will enroll pregnant African American women and their healthy, term infants, to achieve a sample of 300 evaluable infants at 24 months of age. We will collect epidemiological (maternal BMI, gestational weight gain, delivery mode, growth trajectory, antibiotic exposure), behavioral (sucking behavior, feeding practices, diet) and hormonal (appetite and metabolism regulating) parameters known to be associated with childhood obesity, as well as stool and plasma to analyze gut microbiota and the plasma metabolome. We will use mediation analysis to integrate known epidemiologic risk factors, intestinal microbiota, and metabolomic and hormonal biomarkers to identify potential mechanisms and modifiable factors underlying early excess weight gain. We hypothesize that early introduction of foods and non-recommended types of complementary foods will be associated with alterations in gut microbiota, the metabolome and hormonal milieu, resulting in early rapid weight gain in infancy and excess weight gain by age 2years. These findings will provide new insights into factors influencing childhood obesity, will serve to generate hypotheses for more mechanistic studies, and will likely have significant clinical utility in developing effective obesity prevention strateies in this critical developmental stage.

PUBLIC HEALTH RELEVANCE: Rapid weight gain in the first 4 to 6 months of life is associated with obesity later in childhood, and early life is an ideal time for obesity prevention measures because of frequent contact with health care providers and parental control over infant diet. Recent studies in animals and humans demonstrate cause-and-effect relationships between gut bacteria, their metabolites, and obesity development. This longitudinal prospective study of African American children ages birth to 24 months of age, will determine whether the development of gut microbiota and its metabolome predict excess weight gain during this young age, as well as other epidemiological and behavioral factors that may have an interactive role.