Abstract
Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2–7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.
Highlights
Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome
Among the children who received macrolides in early life, we find a positive correlation between overall lifetime antibiotic use and body mass index (BMI), as well as an increased risk of asthma, suggesting that macrolide use may alter the microbiota in infants in a way that predisposes to antibiotic-associated weight gain and asthma in later childhood
Microbiota composition correlates with macrolide use
Summary
Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. The early development of the microbiota differs between antibiotic-treated and non-treated infants[15,16], but nothing is currently known about the long-term associations between lifetime antibiotic use and the intestinal microbiome in children. In Finland, the Social Insurance Institute maintains a national database on prescription drug purchases and eligibility for special reimbursement due to chronic diseases linked with personal identification information of the patient[18] We utilize this unique database and pyrosequencing of fecal microbiomes to investigate the short- and long-term effects of antibiotics on pre-school children’s intestinal microbiome and health. Among the children who received macrolides in early life, we find a positive correlation between overall lifetime antibiotic use and body mass index (BMI), as well as an increased risk of asthma, suggesting that macrolide use may alter the microbiota in infants in a way that predisposes to antibiotic-associated weight gain and asthma in later childhood
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