Epigenetic Mechanisms linking Pre-conceptional Nutrition and Health Assessed in India and Sub-saharan Africa

Deficiencies in essential vitamins and minerals (micronutrients) arising from poor quality diets are a major public health problem in low-and-middle-income countries (LMICs). In pregnant women, they impair fetal development and cause childhood stunting and there is evidence that they also cause long-term problems in the offspring including poor brain and muscle development, increased body fat, and adult heart disease and diabetes.

epigenetics graphic

A baby’s risk of disease is influenced from the first few days after conception. Credit: Felicia Webb

The Nutrition Theme of MRC Unit The Gambia has found evidence that the nutritional environment experienced by a developing embryo around the time of conception may leave a lasting mark on the offspring’s epigenome. This suggests that epigenetic mechanisms may in part underpin the observed long-term adverse health effects arising from suboptimal nutrition in early life.

To help further this research, in June 2015 the Nutrition Theme was awarded a substantial Newton Fund grant to study Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa (EMPHASIS). The Newton Fund grant was jointly awarded to MRC Unit The Gambia, the MRC Lifecourse Epidemiology Unit (LEU) at the University of Southampton and the Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India.

The joint initiative is led by Professor Caroline Fall from the MRC LEU in the UK, with Co-PIs Dr Giriraj Chandak from CCMB in India and Dr Matt Silver from MRC Unit, The Gambia. The grant also includes funds to train a Gambian bioinformatician who will conduct the fieldwork and then study for an MSc in Bioinformatics in the UK. In a competitive process, Modupeh Betts was selected. Modupeh previously worked as a Scientific Officer in the molecular microbiology laboratory in Fajara.

The Gambian arm of the study benefits from MRC Unit The Gambia’s ability to maintain and follow up long term birth cohorts in the West Kiang region. The 3-year Gambian study which is led by Dr Matt Silver will follow up children aged 8-9 years whose mothers took part in the West Kiang Peri-conceptional Multiple Micronutrient Supplementation Trial. Nutrition-responsive epigenetic markers will be correlated with a range of health-related outcomes, including changes in body composition, cardio-metabolic risk markers and cognitive function. A major strength of the study is the ability to compare findings across Indian and Gambian cohorts.

EMPHASIS 1

Figure: Analysis of associations between DNA methylation loci and phenotypic measures in India & The Gambia

The collection of DNA from 350 Gambian children started in Jan 2016. Similar samples are currently being collected from a large intervention trial in Mumbai (n=1100) and the EMPHASIS team will analyse both cohorts in parallel to assess whether the interventions changed the epigenomes of the offspring and whether this predicts health and metabolic outcomes (see Figure 1). The second round of clinic visits for Gambian participants to assess their growth and cognition development will follow later this year.

According to Gambian lead investigator Dr Matt Silver, ‘this is just one component of a heavy investment by the Nutrition Theme into understanding how a mother’s diet prior to conception affects the epigenetic programming of health and development. Our ultimate goal is to design and implement next-generation nutritional supplements that will optimise the early development of the fetus, and hence provide life-long benefits.’