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Allergic asthma is an increasingly common disease and the leading cause of chronic illness in children. Studies on environmental influences and childhood allergy lead David Strachan in 1989 to propose the Hygiene Hypothesis, which states that a lack of early childhood exposure to microbes may increase allergy susceptibility. Though the Hygiene Hypothesis has transformed perceptions in the field of allergy, it still does not explain how other factors such as maternal allergy, stress, dietary changes and tobacco smoke can also alter disease risk. Similarly timed with the formation of the Hygiene Hypothesis, research by Barker on birth weight and heart disease provided the basis for the Developmental Origins of Health and Disease (DOHaD) Hypothesis. Combining the concepts of developmental plasticity and early programming, DOHaD suggests that environmental exposures during foetal and/or neonatal development also influence the development of diseases later in life. We use both human pregnancy cohorts and mouse models to understand the complicated mechanisms involved in prenatal immune modulation and offspring allergy susceptibility.

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Epidemiological Research

Maternal mental health during the COVID-19 pandemic: Effect of the Pandemic on Pregnancy Outcomes and Childhood Health (EPPOCH)

We have recently established a pregnancy cohort in the UK, with the goal of measuring the effect of stress during the COVID-19 pandemic on maternal mental health and childhood health outcomes i.e. the development of allergies in early life (www.eppoch-uk.org). Study recruitment consists of a 45-minute intake questionnaire regarding demographics and medical information as well as validated questionnaires on maternal stress and anxiety during pregnancy. From June to November 2020 we enrolled 3600 participants. Children from our cohort will be followed up until 6 years of age. In a sub-cohort of the study,we are collecting stool samples from mother-infant dyads to investigate how stress affects the gut microbiome. Our cohort is an international sister study to the Pregnancy During the Pandemic Study (PDP), established in Calgary, Canada, that currently has over 5000 participants (www.pregnancyduringthepandemic.com). The EPPOCH and PDP cohorts will use identical questionnaires in the UK and Canada respectively, allowing a global comparison of the mental health experience of pregnant women during the COVID-19 pandemic in culturally similar countries with major differences in the number of cases per capita and governmental response.
 

Mouse Research

Prenatal protection against asthma by the non-pathogenic bacteria Acinetobacter lwoffii

Supporting both the Hygiene and DOHaD hypotheses; both human and animal studies associate prenatal and early childhood exposure to farm-related microbes with protection against allergy. Acinetobacter lwoffii is a non-pathogenic bacteria which is found in high quantities at farming sites. Using a mouse model that closely mimics prenatal microbial exposures in the traditional farming situation, our previous work demonstrated that when pregnant mice were intranasally exposed to A. lwoffii, the asthma phenotype in the progeny was prevented to a large extent. This protection was dependent on maternal Toll-like receptors and the subsequent maternal immune response during gestation. We are working to better understand the mechanisms involved in prenatal protection against allergy using flow cytometry, antibody glycosylation and epigenetic analyses.

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Antibiotic use during pregnancy as a risk factor for asthma in the offspring

In addition to providing protection, prenatal exposures can also contribute to allergy risk in offspring. Antibiotic use during pregnancy increases the risk for offspring allergy development, and since 25% of pregnant women are prescribed antibiotics, it is important to understand the mechanisms behind this phenomenon.  We have recently developed a mouse model of antibiotic exposure during pregnancy that is associated with increased offspring asthma severity. We are currently using this model with an overarching goal of identifying sensitive developmental time points that are influenced by changes in the maternal gut microbiome that may contribute to offspring allergy risk.

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