期刊
MBIO
卷 10, 期 6, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/mBio.02820-19
关键词
Citrobacter rodentium; pathogen-induced colitis; gastrointestinal microbiota; host resistance; murine model; bioluminescence; colonic inflammation; antibiotics
类别
资金
- NYUMC Genome Technology Center (cancer center support grant at the Laura and Isaac Perlmutter Cancer Center) [P30CA016087]
- CHU Hopitaux de Bordeaux
- Philippe Foundation
- NIH [U01 A122285]
- ASM Undergraduate Research Fellowship
- CD Fund
- Transatlantic Program of the Fondation Leducq
- Zlinkoff Foundation
- Groupe Pasteur Mutualite
- SGBSO (Societe de geriatrie de Bordeaux et du Sud Ouest)
Early-life antibiotic exposure may provoke long-lasting microbiota perturbation. Since a healthy gut microbiota confers resistance to enteric pathogens, we hypothesized that early-life antibiotic exposure would worsen the effects of a bacterial infection encountered as an adult. To test this hypothesis, C57BL/6 mice received a 5-day course of tylosin (macrolide), amoxicillin (beta-lactam), or neither (control) early in life and were challenged with Citrobacter rodentium up to 80 days thereafter. The early-life antibiotic course led to persistent alterations in the intestinal microbiota and even with pathogen challenge 80 days later worsened the subsequent colitis. Compared to exposure to amoxicillin, exposure to tylosin led to greater disease severity and microbiota perturbation. Transferring the antibiotic-perturbed microbiota to germfree animals led to worsened colitis, indicating that the perturbed microbiota was sufficient for the increased disease susceptibility. These experiments highlight the long-term effects of early-life antibiotic exposure on susceptibility to acquired pathogens. IMPORTANCE The gastrointestinal microbiota protects hosts from enteric infections; while antibiotics, by altering the microbiota, may diminish this protection. We show that after early-life exposure to antibiotics host susceptibility to enhanced Citrobacter rodentium-induced colitis is persistent and that this enhanced disease susceptibility is transferable by the antibiotic-altered microbiota. These results strongly suggest that early-life antibiotics have long-term consequences on the gut microbiota and enteropathogen infection susceptibility.
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