Modulation of DNA methylation states and infant immune system by dietary supplementation with ω-3 PUFA during pregnancy in an intervention study

Background: Early-life exposures to tobacco smoke and some dietary factors have been identified to induce epigenetic changes in genes involved in allergy and asthma development. Omega-3 (n-3) polyunsaturated fatty acid (PUPA) intake during pregnancy could modulate key cytokines and T helper (Th) cell maturation; however, little is known about the mechanism by which omega-3 PUPA could have a beneficial effect in preventing inflammatory disorders. Objective: We sought to test whether prenatal dietary supplementation with omega-3 PUPA during pregnancy may modulate epigenetic states in the infant immune system. Design: This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg docosahexaenoic acid (DHA) or a placebo from 18 to 22 wk of gestation to parturition. We applied quantitative profiling of DNA methylation states in Th1, Th2, Th17, and regulatory T relevant genes as well as LINE1 repetitive elements of cord blood mononuclear cells (n = 261). Results: No significant difference in promoter methylation levels was shown between omega-3 PUPA-supplemented and control groups for the genes analyzed; however, omega-3 PUPA supplementation was associated with changes in methylation levels in LINE] repetitive elements (P = 0.03) in infants of mothers who smoked during pregnancy. Furthermore, an association between the promoter methylation levels of IFN gamma and IL13 was modulated by omega-3 PUPA supplementation (P = 0.06). Conclusions: Our results indicate that maternal supplementation with omega-3 PUPA during pregnancy may modulate global methylation levels and the Th1/Th2 balance in infants. Therefore, the epigenetic mechanisms could provide attractive targets for prenatal modulation and prevention of inflammatory disorders and potentially other related diseases in childhood and adulthood.