135. Early-life Pulsed Antibiotic Treatment as a Contributor to Enhanced Weight Gain and Bone Growth in Mice
Session: Oral Abstract Session: Bacterial Pathogenesis and Virulence
Friday, October 21, 2011: 9:30 AM
Room: 151AB

Background: Over the past decades, children in developed countries have shown dramatic increases in height and in weight and obesity. Increasing evidence suggests that gut microbial composition affects growth. Antibiotics, which perturb the microbiome, are widely used to promote weight gain in farm animals. This effect is strongest when exposure begins early in life. Childhood antibiotic use may thus provide an explanation for population increases in height and obesity.

Using a mouse model designed to mimic pediatric antibiotic use, we tested the hypothesis that short, therapeutic-dose antibiotic pulses administered early in life will sufficiently change the gut microbiome to contribute to enhanced growth.

Methods: C57BL/6J female mice received three early-life pulses of therapeutic-dose antibiotics via their drinking water. The four study groups received either no antibiotics (control) or pulses of tylosin, amoxicillin, or alternating tylosin and amoxicillin. Mice were weighed throughout the experiment and periodically analyzed by Dual-Energy X-ray Absortiometry to monitor changes in mass distribution and bone composition. Quantitative-PCR of DNA extracted from fecal pellets was used to monitor the gut microbiome.

Results: Early-life pulsed antibiotic treatment (PAT) significantly increased growth rate and body composition, with the most pronounced effects observed shortly after treatment. The average early-life growth rate of all PAT mice was 6.9% higher than control (p<0.001). The average total mass, lean mass, bone mineral content, and bone area of all PAT mice were significantly higher than control at multiple time points, with maximum increases of 8.1% (p<0.01), 11.0% (p<0.001), 11.6% (p<0.01), and 8.6% (p<0.001), respectively. PAT also significantly altered the gut microbiome. In PAT mice, there was a 0.18 log10 reduction in total number of bacteria relative to control shortly after PAT (p<0.05), but the total bacterial numbers normalized by day 135 of life.

Conclusion: PAT affects weight gain, bone development, and numbers of total bacteria in mice. Intensive early-life antibiotic use among human children may similarly contribute to trends in growth by altering the microbiome.


Subject Category: B. Bacterial pathogenesis, studies in animal models, molecular pathogenicity

Yael Nobel1, Laura Cox2, Isabel Teitler1 and Martin Blaser, MD, FIDSA3, (1)Medicine, New York University Medical Center, New York, NY, (2)Microbiology, New York University Medical Center, New York, NY, (3)VA New York Harbor Healthcare System and NYU School of Medicine, New York, NY

Disclosures:

Y. Nobel, None

L. Cox, None

I. Teitler, None

M. Blaser, None

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