Dietary shaping of the early life metabolome and its role in healthy lung and brain development

ended

Asthma and behavioral problems related to neurodevelopmental delay such as ADHD and autism are common childhood disorder with lack of insight in disease mechanisms and no preventive measures, which is an unmet medical and societal need. In the Danish COPSAC mother-child cohort, I showed in two randomized trials that pregnancy supplements with n-3 long-chained polyunsaturated fatty acids (n-3 LCPUFA) and high-dose vitamin D reduced offspring asthma risk, improved cognitive scores and accelerated language and milestone achievement, which was replicated in the American VDAART vitamin D trial. This holds the promise for primary prevention but establishing underlying biochemical mechanisms and effect modification by maternal and early life diet and host genetics remains to achieve a personalized preventive strategy targeting supplements only to those women, whose offspring will benefit from it. This research project aims to understand how dietary supplements and diet in pregnancy and early life shapes the child’s metabolism and how this is linked to asthma and neurodevelopment, using longitudinal untargeted and targeted metabolomics profiles from more than 1,500 mother-child pairs in COPSAC and VDAART, detailed data on maternal and infant diet, the early life exposome, and genetics and genomics data. The objective is to identify metabolites and biochemical pathways of importance for asthma and neurodevelopment, focusing on n-3/n-6 LCPUFAs, sphingolipids and tryptophan, with the ultimate goal to achieve healthy lung and brain development through personalized diet interventions during pregnancy. The transdisciplinary study group lead by the applicant consisting of MDs with pediatric, respiratory and psychiatric expertise, wet and dry lab metabolomics experts and bioinformaticians will bridge basic and clinical sciences in an international collaboration between COPSAC, Denmark, and VDAART at Harvard Medical School, US.