Dietary methyl donors and epigenetics
Evidence is rapidly accruing that some life-course and intergenerational influences on human health may be mediated by epigenetic modification of DNA. Animal models clearly show that offspring phenotype can be strongly modulated by maternal supplementation with methyl-donor rich diets given pre-conceptually and in pregnancy. It is thought that analogous mechanisms may operate in humans, and if so, they would have profound implications in terms of understanding the basic biology of the developmental origins of disease, and of translating this into diet-based interventions. We are carrying out several projects in The Gambia to investigate epigenetic mechanisms in humans.
Our project on “Methyl donors and epigenetics” assesses potential differences in methyl-donor intake created by the annual Gambian wet/hungry and dry/harvest seasons, and examines whether maternal dietary deprivation around the time of conception results in differences in biomarkers for methyl-donor supply in mothers, and in DNA methylation in their babies. The dietary assessment of methyl donor content of foods, i.e. substances involved in one-carbon metabolism, is carried out for in collaboration with Prof Steven Zeisel’s lab. Prof Sheila Innis is our partner for the analysis of a comprehensive set of biomarkers including folate, choline, betaine, B vitamins, methionine and other metabolites of the one-carbon metabolism (i.e. homocysteine, SAM and SAH) in pregnant women. B2 analysis is carried out at MRC Human Nutrition Research in Cambridge. Collaboration with Prof Rob Waterland’s group has already established that there is variation in global DNA methylation in metastable epiallelles in individuals conceived in the hungry or harvest season (see publications). Preliminary work with colleagues at the University of Leeds and the IARC in Lyon is also underway to assess possible effects of in utero aflatoxin exposure on epigenetic changes. We are currently following on and expanding the analysis of DNA methylation patterns by season of conception and maternal nutritional status in a larger number of babies.
In collaboration with colleagues at Cambridge we have used both candidate gene and whole genome methylation analysis to demonstrate that periconceptional multiple micronutrient supplementation affects methylation status in complex and sex-specific ways.