The Neonatal Methylome as a Gatekeeper in the Trajectory to Childhood Asthma

Abstract

Asthma is a heterogeneous group of conditions that typically begin in early life and result in recurrent, reversible bronchial obstruction. The role played by epigenetic mechanisms in the pathogenesis of childhood asthma is understood only in part. Here we discuss asthma epigenetics within a developmental perspective based on our recent demonstration that the epigenetic trajectory to childhood asthma begins at birth. We next discuss how this trajectory may be affected by prenatal environmental exposures. Finally, we examine in vitro studies that model the impact of asthma-associated exposures on the epigenome. All of these studies specifically surveyed human DNA methylation and involved a genome-wide component. In combination, their results broaden our understanding of asthma pathogenesis and the role the methylome plays in this process.

Sex Bias in Asthma Prevalence and Pathogenesis

“…Gene transcription can be altered by epigenetic modifications that are established in utero or developed due to environmental exposures, disease states, antibiotic or medication use, and lifestyle choices. Alterations in the epigenome in utero or during childhood may also drive asthma development (54, 55). Maternal smoking alters DNA methylation and maternal smoking is a known risk factor for childhood asthma.…”

Introductory Chapter: Impact of First 1000 Days Nutrition on Child Development and General Health

“…That study underscores the potential for early life environmental stressors to cause longterm epigenetic modifications. Prenatal exposure to other environmental stressors on the mother, such as smoking, asthma, immune stress during pregnancy, and obesity, are associated with differences in the DNA methylation patterns of peripheral blood cells when comparing children who develop asthma with those who do not develop the condition [85].…”

Changes in peripheral immune populations during pregnancy and modulation by probiotics and ω-3 fatty acids

“…Thus, loss of protective features or presence of new risk factors must cause the increasing prevalence of these diseases since the middle of the last century 2 – 6 . A reduced amount and diversity of microbial encounters and a decreased dietary ω-3-/ω-6 long-chain polyunsaturated fatty acid ratio could be one of the key factors in the development of a deviated immune maturation 7 , 8 . Based on these hypotheses, both probiotics and ω-3 fatty acids have been used in infant allergy prevention trials 9 – 13 .…”