Antibiotic use during pregnancy increases offspring asthma severity in a dose‐dependent manner

Alhasan, Moumen M.; Cait, Alissa; Heimesaat, Markus M.; Blaut, Michaël; Klopfleisch, Robert; Wedel, Alexander; Conlon, Thomas M.; Yildirim, Ali Önder; Sodemann, Elisa B.; Mohn, William W.; Bereswill, Stefan; Conrad, Melanie L.

doi:10.1111/all.14234

Cited by 58 publications

(58 citation statements)

References 37 publications

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“…Therefore, by inducing reduction and modification of the infant intestinal microbiota, early pregnancy antibiotic exposure may influence on immunological development, leading to an increase of the potential of chronic disease 42,53 . In an animal study, maternal vancomycin treatment during pregnancy increased offspring allergic lung inflammation 54 . Milliken et al 55 reported that maternal use of antibiotics during the antenatal or labor could cause intestinal dysbiosis and particularly reduced diversity of Lactobacillus and Bifidobacterium .…”

Section: Discussionmentioning

confidence: 99%

Maternal antibiotic exposure during pregnancy and the risk of allergic diseases in childhood: A meta‐analysis

Zhong

Zhang

Wang

et al. 2020

Pediatric Allergy Immunology

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Background: Increasing studies suggest that antibiotic exposure during pregnancy may increase the risk of childhood allergic diseases; however, controversy still exists. Thus, we conducted this meta-analysis to evaluate the association between antibiotic use during pregnancy and childhood asthma/wheeze, eczema/atopic dermatitis, and food allergy. Methods: CENTRAL, EMBASE, and PubMed were searched for studies up to July 20, 2020. Cohort studies and case-control studies that estimated the association of antibiotic exposure in pregnancy with the risk of childhood asthma/wheeze, eczema/ atopic dermatitis, and food allergy were included. A random-effects model or fixedeffects model was used to calculate the pooled estimates. The quality of the included studies was assessed by the Newcastle-Ottawa Scale (NOS). Stata12.0 software was used to analyze the association through a meta-analysis. Results: A total of 26 studies were included in the meta-analysis. The results showed that maternal antibiotic exposure in pregnancy and the summary OR for the risk of childhood asthma/wheeze was 1.29 (95% CI = 1.16-1.43), the summary OR for eczema/atopic dermatitis was 1.62 (95% CI = 1.16-2.27), and the pooled OR for food allergy was 1.36 (95% CI = 0.94-1.96). Conclusions: Our results indicated that maternal antibiotic use during pregnancy might increase the risk of asthma/wheeze and eczema/atopic dermatitis but not food allergy in children. Further studies with larger sample size and robust multivariable adjustment are needed to confirm our findings. Nevertheless, the appropriate use of antibiotics during pregnancy is incredibly important, and healthcare professionals should be selective when prescribing antibiotics for pregnant women.

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Section: Discussionmentioning

confidence: 99%

Maternal antibiotic exposure during pregnancy and the risk of allergic diseases in childhood: A meta‐analysis

Zhong

Zhang

Wang

et al. 2020

Pediatric Allergy Immunology

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“…Pulmonary microbial dysbiosis can influence the inflammation status of the host. The dysbiosis can be inherited, if the mother was treated with antibiotics during the pregnancy resulting in higher asthma rates in the offspring as shown by Alhasan et al 57 Surprisingly, instead of the expected upregulation of type 2 cytokines in allergic offspring, a downregulation was found. Causalities are still unclear and will require specifically designed future studies to address this issue.…”

Section: Microbial Dysbiosis and Asthmamentioning

confidence: 96%

Advances and recent developments in asthma in 2020

Cevhertas

Öğülür

Maurer

et al. 2020

Allergy

117

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In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis, and treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis, and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping, and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/ multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers, are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS-CoV-2, and COVID-19.

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“…22 The use of antibiotics by mothers during pregnancy increases the risk of asthma in their offspring. 23 Hence, some asthma-related immune markers in mothers and their offspring were examined in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Intestinal immune homeostasis is affected by the composition of the symbiotic microbial community, 21 and the mother's microbial environment may affect the early formation of the fetal immune system 22 . The use of antibiotics by mothers during pregnancy increases the risk of asthma in their offspring 23 . Hence, some asthma‐related immune markers in mothers and their offspring were examined in mice.…”

Section: Discussionmentioning

confidence: 99%

Maternal microbiome regulation prevents early allergic airway diseases in mouse offspring

Liu

et al. 2020

Pediatric Allergy Immunology

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Background: Asthma is a serious global health problem, severely affecting the lives of sufferers and their families. An exceptionally hygienic home and reduced microbial exposure can aggravate the incidence of childhood asthma. Methods: Specific-pathogen-free BALB/c mice were pre-treated with bacterial lysate (BL; 1 mg/kg) as a high microbial load maternal mouse model, and then, the offspring mice were established as an allergic airway disease (AAD) model. The expression levels of TLR2, TLR4, and HDAC9 in the mother's intestine and the offspring's lungs were detected. Relevant indicators of regulatory T cells (Tregs) were identified in the mother and offspring mice. The changes in the expression of Th1-, Th2-, Th9-, and Th17-related cytokines in the offspring mice were evaluated among different pretreated groups. Results: After augmenting the mothers' intestinal microbiota through oral BL gavage, the expression of TLR2 and TLR4 in the colon mucosa and colon lymphoid tissues was enhanced and that of HDAC9 in the colon mucosa was decreased, and the proportion of spleen Tregs was increased. The offspring showed similar changes in the AAD model compared with the offspring of the control-group mothers: TLR2 and TLR4 expression in the lungs and the proportion of spleen Tregs increased, HDAC9 expression in the lungs decreased, and AAD-induced airway pathologic characteristics were reversed; additionally, Th1/Th2 and Th9 imbalances were rectified. Conclusions: This study presents a new framework for the prevention of childhood asthma, elucidating the mechanism of regulating the mother's intestinal microbiome to protect the offspring's early asthma via animal experiments.

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Antibiotic use during pregnancy increases offspring asthma severity in a dose‐dependent manner

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 58 publications

References 37 publications

Maternal antibiotic exposure during pregnancy and the risk of allergic diseases in childhood: A meta‐analysis

Maternal antibiotic exposure during pregnancy and the risk of allergic diseases in childhood: A meta‐analysis

Advances and recent developments in asthma in 2020

Maternal microbiome regulation prevents early allergic airway diseases in mouse offspring

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