Alison McCormick

Introduction. More than one in six children ages 2-19 in the United States are obese¹. Childhood obesity is a serious health issue associated with psychosocial comorbidities and an increased risk of adverse health outcomes later in life¹. Because obesity can be viewed as a chronic, incurable disease, prevention is the best solution, especially in children². Obesity results from a metabolic imbalance between energy intake and expenditure. Thus, factors that influence metabolism, such as the composition of the gut microbiome, should be considered as potential targets for obesity prevention¹ The composition of the gut microbiome is influenced by factors including mode of delivery at birth, diet, and antibiotic usage.³ Some studies have indicated that repeated exposure to antibiotics early in life is associated with increased incidence of childhood obesity.⁴ Given the important role that the gut microbiome plays in metabolism, it is plausible that antibiotics exert this effect by altering the gut microbiome. The purpose of this review is to elucidate potential mechanisms by which antibiotics may alter the gut microbiome and contribute to childhood obesity so that protocols may be developed to prescribe antibiotics in such a way that this adverse effect can be prevented. Methods. Studies were conducted in both mouse models and children. The mouse models were administered therapeutic doses of antibiotics in the first 28-40 days of life and were then assessed for body composition, growth rate, metabolic hormones, lipid metabolism, and microbiome composition.^5,6 The studies involving children utilized health records to determine past antibiotic exposure and assess the development of obesity and gut microbiome composition.^7,8 Results. Early-life antibiotic exposure is associated with increased fat mass, increased lipid synthesis, decreased expression of genes involved in fatty acid and carbohydrate metabolism, and altered microbiome composition.^5-8 In children, exposure to antibiotics in the first 2 years of life is associated with the development of obesity by age 5.⁸ Observed changes in host metabolism persist even after microbiome composition returns to normal.⁵ Broad spectrum and macrolide antibiotics have more pronounced effects than narrow spectrum and beta-lactam antibiotics.^5,7,8 Conclusion. Exposure to antibiotics during critical development periods increases the risk for childhood obesity. This affect is mediated by antibiotics altering the gut microbiome, which has profound, long-lasting effects on host metabolism. Given these findings, it is likely that the prevalence of childhood obesity could be reduced by limiting the use of broad spectrum antibiotics in the first two years of life.

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