Prenatal influences on offspring allergy

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. Using mouse models of prenatal protection or risk for asthma in the offspring, our lab is working to unravel the complicated mechanisms involved in prenatal immune modulation and offspring allergy susceptibility.

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.  

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 microbiome that may contribute to offspring allergy risk.

Maternal asthma during pregnancy alters offspring asthma risk in an allergen dependent manner

In addition to the genetic risk that maternal asthma transfers to the offspring, maternal allergic responses during pregnancy can also contribute to offspring asthma susceptibility.  We have designed a mouse model of maternal asthma during pregnancy that alters different aspects of offspring asthma development according to the type of maternal allergy.  We are currently using this model to understand how the prenatal environment differentially affects offspring asthma.