Pneumologie 2020; 74(S 01): 73
DOI: 10.1055/s-0039-3403219
Freie Vorträge (FV07) – Sektion Zellbiologie
From bench to bedside
Georg Thieme Verlag KG Stuttgart · New York

Administering antibiotics during pregnancy increases offspring asthma severity in a dose-dependent manner

M Alhasan
1   Charité – Universitätsmedizin Berlin, Institute for Microbiology, Infectious Diseases and Immunology
,
A Cait
2   Department of Microbiology and Immunology, University of British Columbia
,
M Heimesaat
3   Institute of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, Corporate Member of Free University of Berlin, Humboldt University of Berlin and Berlin Institute of Health
,
M Blaut
4   Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Germany
,
R Klopfleisch
5   Department of Veterinary Medicine, Free University of Berlin
,
TM Conlon
6   Comprehensive Pneumology Center (Cpc), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (Dzl)
,
A Yildirim
6   Comprehensive Pneumology Center (Cpc), Institute of Lung Biology and Disease, Helmholtz Zentrum München, Member of the German Center for Lung Research (Dzl)
,
EB Sodemann
7   Charité – Universitätsmedizin Berlin
,
S Bereswill
3   Institute of Microbiology, Infectious Diseases and Immunology, Charité – Universitätsmedizin Berlin, Corporate Member of Free University of Berlin, Humboldt University of Berlin and Berlin Institute of Health
,
M Conrad
1   Charité – Universitätsmedizin Berlin, Institute for Microbiology, Infectious Diseases and Immunology
› Author Affiliations
Further Information

Publication History

Publication Date:
28 February 2020 (online)

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    Introduction: Many retrospective studies have linked asthma, the leading chronic disease in children worldwide, with antibiotic use during pregnancy or in early life. However, neither the causal relationship nor the possible mechanisms have been clearly defined. Additionally, existing mouse models treat both mothers and offspring with antibiotic, making it difficult to investigate the maternal/prenatal contribution to offspring asthma susceptibility. To deal with these issues, we designed a model where treatment of mothers with antibiotic only during pregnancy results in increased offspring asthma severity.

    Methods: BALB/c mice were mated and treated orally from gestation day 8 to 17 with vancomycin; three different vancomycin concentrations were tested and control mothers were treated with water. At weaning offspring were sensitized and challenged with OVA using an experimental asthma protocol. To assess the asthma phenotype, serum antibodies, bronchoalveolar lavage cell counts, airway reactivity, lung tissue inflammation and lung tissue goblet cells were analysed. Gut microbiota analysis was performed using both maternal and offspring faeces. Offspring caecum content was taken for short chain fatty acid analysis.

    Results: Allergic offspring from vancomycin treated mothers showed increased allergic airway inflammation compared to allergic offspring from control mothers. This was evidenced by, increased: airway reactivity, BAL cell counts, lung tissue inflammation and goblet cells, however, no significant differences were found in serum antibodies. Analysis of the intestinal microbiota revealed microbial dysbiosis in the mothers that was mirrored in the offspring at weaning and after allergy induction. This microbial dysbiosis was associated with significantly reduced caecal SCFA concentrations in allergic offspring.

    Conclusion: There is a dose-dependent correlation between the administration of antibiotics during pregnancy and increased asthma severity in offspring transgenerational microbial dysbiosis and subsequent reduction in offspring SCFA levels appear to play a key role in antibiotic use during pregnancy and increased offspring asthma severity.


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