HDHL-Biomarkers: Biomarkers for Infant Fat Mass Development and Nutrition (BioFN)

WHAT: Childhood obesity is a rapidly growing problem. Weight loss programs have limited effects and prevention is our only hope to stem this new epidemic. Infant fat mass development in particular, has long-term effects on later body fat mass and thus metabolic health. Lipid profiles may be used as biomarkers for fat mass development and provide predictive biomarkers for later childhood obesity.

WHO:
BioFN brings together experts on:
- Lipidomics (Dr Albert Koulman, University of Cambridge, UK);
- Paediatric endocrinology (Prof Anita Hokken-Koelega, Erasmus University, NL; Prof David Dunger and Dr Ken Ong, University of Cambridge, UK)
- Systems biology (Dr Henrik Bjoern Nielsen, Clinical Microbiomics, DK)
- Lipid metabolism (Dr Lars Hellgren, Danish Technical University, DK).
BioFN is coordinated by Dr Albert Koulman.

HOW:
BioFN will use high-resolution mass spectrometry based lipid profiling in samples from two birth cohort studies, Sophia-Pluto (Rotterdam, NL) and Cambridge Baby Growth Study (UK) that both have very precise body composition data. This will allow us to develop predictive biomarkers for fat distribution. By quantifying the dietary effect on lipid metabolism, gut microbiome metabolism and fat distribution BioFN will provide tools to prevent of childhood obesity.

Development in the early life period has lifelong consequences. Accelerated postnatal weight gain is associated with an adverse metabolic profile and increased obesity risk in adulthood. Height and weight gain are only crude measures and do not take body composition into account. Early visceral fat mass development, in particular, is thought to have long-term effects on later body fat mass and fat distribution, and thus metabolic health. Accurate measurements of fat mass development in infants requires time, skilled personnel and equipment, hence limiting use in routine neonatal care and research.
Our hypothesis is that the differences in fat mass development are associated with differences in lipid metabolism, which are driven by diet and gut microbiome activity in response to diet. We propose that changes in infancy diet results in major changes in the infancy microbiome leading to altered metabolism of macronutrients, especially of lipids. Lipid profiles could be used as biomarkers for fat mass development, microbiome metabolism and reflect growth trajectories. Our aims are to:
1) Develop biomarkers for body fat distribution at 2 years of life;
2) Develop lipid-based biomarkers at an early age to predict body fat distribution at 2 years of age;
3) Develop predictive biomarkers for later childhood (5-10 years) body composition (lean vs. fat) and adipose tissue distribution (subcutaneous vs. visceral);
4) Quantify the dietary effect on lipid metabolism, gut microbiome metabolism and fat distribution using data from infants that receive both breast milk and formula.
Existing detailed anthropometric and food intake data of healthy term infants from the Sophia-Pluto cohort will be combined with extensive lipidomic profiling and data from the BBSRC-DRINC project. This will feed into a custom designed integrative systems biology analyses enabling this consortium to identify, substantiate and confirm biomarkers for fat distribution in this translational project.

Need for innovation: It is well established that early life growth trajectories are associated with later life body composition and metabolic health. The mechanisms responsible for body composition development in infancy and early childhood remain largely unknown. Also, effects of infant feeding on growth trajectories are poorly defined. Progress in this field of research is hampered by the complexity and costs of body composition measurements in young infants and children. Validated biochemical marker patterns for healthy growth and fat mass development would reduce study time, the number of participants and total research costs. This work will make it easier for future academic and industrial studies to investigate effects of different nutrients and nutritional compositions on growth, development, and long-term health.

Relevance for public health: Better and personalized feeding strategies for infants will provide a healthier start of life and therefore reduce their risk of childhood obesity and related disease in later life. This will have a significant impact on future health care costs throughout the life course by reducing the incidence of obesity and metabolic diseases. The BioFN project will explore the clinical application of lipid biomarkers for body fat distribution. With the current surge in childhood obesity and the necessity to act on prevention rather than focussing on weightloss, it is essential to have access to predictive biomarkers. Detailed body fat distribution measurements are not possible in a routine health care, which in many European countries takes place at home. Biomarkers for fat distribution that can be measured from dried blood spots means that almost all infants can be assessed and early prevention of further development of childhood obesity addressed.

Long term aims of the consortium: The clinical application of the biomarkers that we aim to develop in this work will be the hallmark of success for this project. However, it is important to have a realistic view on the timelines of biomarker development validation and clinical application, and moving from differential biomarkers to clinical application, often takes more than 10 years (Koulman et al. 2009). We, therefore, expect that this project will be the first step on this long path. During the second year of the project, we expect to have data showing how strongly these biomarkers can predict fat distribution and later childhood obesity. This will then be used to apply for follow-up funding to start a translational project, with the aim to first validate the findings and further test how changes in diet and behaviour can affect these biomarkers. In addition, the multidisciplinary consortium opens new avenues to extend the strategic international collaboration to better understand the interaction between infancy diet (both milk and weaning foods in young children), adiposity development and lifelong metabolic implications. It allows for follow-up projects including nutritional intervention studies, with the ultimate goal to improve the nutritional quality of infant milks and foods.
Childhood obesity is a rapidly growing problem in many countries across the world. With the limited effect of treatment, prevention is our only hope to stem this new epidemic. Early biomarkers that can predict childhood obesity and early targeted interventions that can improve healthy fat distribution in infants are needed, which underlines the urgency of the BioFN project.