Weighing the Consequences: A Systematic Review and Quantitative Evaluation of Early Childhood Antibiotic Exposure as a Risk Factor for Obesity

Abstract

The human gut microbiota encompasses a diverse ecosystem with hundreds if not thousands of microbial species, with relative proportions of different taxa varying between and within individuals over their lifetimes. Intestinal microbes interact with the central nervous system while playing important roles in host immune and metabolic function. Infants acquire their initial microbiota during delivery, with mature structures and compositions developing during the first few years of life. Early childhood therefore serves as a critical window for microbiota establishment during which the intestinal ecosystem is especially vulnerable to disruption from antibiotics. Research has thus far linked pediatric antibiotic use to chronic conditions such as obesity, metabolic syndrome, irritable bowel syndrome, and asthma. Clinical antibiotics have furthermore been shown to promote the emergence of drug-resistant microbes, compounding serious immediate and long-term consequences for individuals as well as societies.

This systematic review compiles all studies available on PubMed investigating the link between early childhood antibiotic exposure and risk of overweight and obesity. Results were analyzed by exposure conditions thought to influence risk, including age, number of antibiotic courses, sex, and type of antibiotic. Earlier antibiotic administration and greater number of exposures were associated with great risk of weight gain, as were broad-spectrum relative to narrow spectrum antibiotics. Exposed boys were also more severely affected than girls. The overall increased risk of obesity associated with antibiotic exposures was estimated to be 5.7% using a weighted average calculation.

A population attributable fraction of US overweight and obesity to childhood antibiotic exposure was then found to be 0.0447 using the weighted odds ratio and state-level antibiotic prescription data. Combined with existing estimates of the lifetime cost of obesity, it is projected that increased risk of overweight and obesity arising from early childhood antibiotic exposure places a total financial burden of $9,410,487,488.99 on the US healthcare system. The scale of both lifetime costs associated with pediatric obesity and the prevalence of overweight and obesity demonstrate that even a moderate increase in risk would bring about dramatic economic consequences.

This thesis concludes by exploring policy and research priorities for promoting judicious antibiotic practices in clinical and public health contexts. Antibiotic stewardship will be crucial to minimizing risk to patient health as well as the development of antibiotic resistance at both individual and population levels. Finally, it examines a variety of relatively novel research areas aimed at restoring microbiota health after perturbation, including probiotics, fecal transplantation, and phage therapy, among others.