Early Developmental Origins of Disease

The Barker hypothesis states, in general, that early in utero exposure affects disease risk later on in life. While, his work focused on undernutrition leading to coronary heart disease in adulthood, others have expanded this hypothesis. In a review by J. Bousquet et al., it was proposed that fetal genes are allowed to persist through epigenetic mechanism in allergic asthma due to early environmental exposure. Asthma is typically associated with an exaggerated Th2 response. In our class, we learned that during development a fetus has a strong Th2/Th1 imbalance which is rapidly reversed after birth. With the increase in prevalence of asthma in recent years, you can predict that early environmental exposure can alter this normal T helper programming allowing the persistence of the Th2/Th1 imbalance

A recent mouse study analyzed the role that diet during pregnancy plays on enhancing allergic airway disease. Pregnant mice were given a diet with varying amounts of methyl donors. (Methyl donors can alter DNA methylation thus altering gene expression. Folate is a methyl donor which is often supplemented in the diet of pregnant women in developed countries.) Allergic airway disease was then measured in their offspring. They reported that maternal diet alone was enough to enhance the severity of allergic airway disease. The idea that early environmental exposure programs our bodies/immune system to be more susceptible or more resistant to diseases later on in life fascinates me. I look forward to increased research in early programming.

Bousquet et al. Allergy 2004:59:138-147
Hollingsworth et al. J. Clin. Invest. 118:3462-3469 (2008)