Antibiotic use during pregnancy increases offspring asthma severity in a dose‐dependent manner
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- Moumen M. Alhasan
- Institute 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
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- Alissa M. Cait
- Department of Microbiology and Immunology Life Sciences Institute University of British Columbia Vancouver BC Canada
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- Markus M. Heimesaat
- Institute 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
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- Michael Blaut
- Department of Gastrointestinal Microbiology German Institute of Human Nutrition Potsdam‐Rehbruecke Nuthetal Germany
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- Robert Klopfleisch
- Department of Veterinary Medicine Freie Universität Berlin Berlin Germany
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- Alexander Wedel
- Department of Educational Psychology Institute of Education Technische Universität Berlin Berlin Germany
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- Thomas M. Conlon
- Comprehensive Pneumology Center (CPC) Institute of Lung Biology and Disease Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL) Neuherberg Germany
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- Ali Ö. Yildirim
- Comprehensive Pneumology Center (CPC) Institute of Lung Biology and Disease Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL) Neuherberg Germany
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- Elisa B. Sodemann
- Institute 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
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- William W. Mohn
- Department of Microbiology and Immunology Life Sciences Institute University of British Columbia Vancouver BC Canada
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- Stefan Bereswill
- Institute 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
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- Melanie L. Conrad
- Institute 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
説明
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>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.</jats:p></jats:sec>
収録刊行物
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- Allergy
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Allergy 75 (8), 1979-1990, 2020-03-11
Wiley
