BioFN

Background

Childhood obesity is a rapidly growing problem in many countries across the world. Weight loss programs have limited effects and prevention is our only hope to stem this new epidemic. Development in the early life period has lifelong consequences. 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 healthy infants requires time, skilled personnel and specialized equipment, hence limiting implementation in routine neonatal care and research. Our hypothesis remains 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 currently found a range of lipids that show a strong association with body composition at different ages (3m, 12m and 24m).

We proposed that changes in infancy diet results in major changes in the infancy microbiome leading to altered metabolism of macronutrients, especially of lipids. Data on genetically caused differences in breastmilk oligosaccharides are strongly suggesting that the effect of the gut microbiome on lipid metabolism is occurring higher up in the intestinal tract than can be assessed by faecal microbiome analysis. Lipid ratio’s that reflect desaturase and elongase activity are predictive of growth and weight gain. We are therefore rapidly covering our aims:

Aim

The aims of this project were to:

1. Develop biomarkers for body fat distribution at 2 years of life; A series of candidate biomarkers is currently under investigation and will be further validated.
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 usingdata from infants that receive both breast milk and formula (mixed feeding).

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. These results will be feed into a custom-designed integrative systems biology analyses which has been established. This allows the consortium to identify, substantiate and confirm biomarkers for fat distribution in this translational project that aims to provide new tools to help to prevent childhood obesity.

Expected impact

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 weight loss 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 biomarker 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.