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Published on: August 7, 2017
Antibiotic use during pregnancy increases offspring asthma severity in a dose-dependent manner
Moumen M Alhasan1,2, Alissa M Cait3, Markus M Heimesaat1
1Institute of Microbiology, Infectious Diseases and Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.
Insights
Antibiotic use in pregnancy increases offspring asthma risk. This study in mice shows maternal vancomycin alters the gut microbiome and lowers beneficial short-chain fatty acids, leading to more severe allergic lung inflammation in pups.
Area of Science:
- Immunology
- Microbiome Research
- Developmental Biology
Background:
- Antibiotic exposure during pregnancy is linked to higher asthma risk in children.
- Understanding the mechanisms behind this association is crucial due to high antibiotic prescription rates in pregnant women.
- No prior studies have experimentally investigated this link.
Purpose of the Study:
- To establish a mouse model to study the effects of antibiotic treatment during pregnancy on offspring asthma susceptibility.
- To investigate the dose-dependent effects of vancomycin on asthma severity in offspring.
- To analyze changes in the gut microbiome and short-chain fatty acids.
Main Methods:
- Pregnant mice received daily oral vancomycin at three different doses.
- Offspring were exposed to ovalbumin to induce experimental asthma.
- Gut microbiome composition and short-chain fatty acid levels were analyzed in mothers and offspring.
Main Results:
- Maternal vancomycin treatment during pregnancy led to increased offspring asthma severity in a dose-dependent manner.
- Significant alterations in gut microbiome composition were observed in both mothers and pups.
- Decreased concentrations of short-chain fatty acids in pups correlated with increased asthma severity.
Conclusions:
- Maternal antibiotic exposure during pregnancy influences the neonatal gut environment.
- This exposure increases susceptibility to allergic lung inflammation in offspring.
- Findings support the Developmental Origins Hypothesis regarding environmental influences on health.
Background:
The use of antibiotics during pregnancy is associated with increased allergic asthma risk in the offspring, and given that approximately 25% of pregnant women are prescribed antibiotics, it is important to understand the mechanisms contributing to this phenomenon. Currently, there are no studies that directly test this association experimentally. Our objective was to develop a mouse model in which antibiotic treatment during pregnancy results in increased offspring asthma susceptibility.
Methods:
Pregnant mice were treated daily from gestation day 8-17 with an oral solution of the antibiotic vancomycin, and three concentrations were tested. At weaning, offspring were subjected to an adjuvant-free experimental asthma protocol using ovalbumin as an allergen. The composition of the gut microbiome was determined in mothers and offspring with samples collected from five different time points; short-chain fatty acids were also analyzed in allergic offspring.
Results:
We found that maternal antibiotic treatment during pregnancy was associated with increased offspring asthma severity in a dose-dependent manner. Furthermore, maternal vancomycin treatment during pregnancy caused marked changes in the gut microbiome composition in both mothers and pups at several different time points. The increased asthma severity and intestinal microbiome changes in pups were also associated with significantly decreased cecal short-chain fatty acid concentrations.
Conclusion:
Consistent with the "Developmental Origins Hypothesis," our results confirm that exposure to antibiotics during pregnancy shapes the neonatal intestinal environment and increases offspring allergic lung inflammation.
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