Systems approaches to understand the mechanisms of malnutrition

Severe malnutrition, especially in children, remains a public health burden that requires urgent scientific consideration. More than 35% of all deaths among children under 5 years old worldwide are directly or indirectly attributed to malnutrition. Despite careful monitoring, undernourished children often are at high risk of death, and for those who survive, suffer long-term consequences such as growth faltering and increased risk of developing non-communicable diseases. Understanding the main mechanisms regulating metabolic dysregulation during malnutrition would enable us to address these issues more effectively.

The overarching goal within our group is to understand the molecular mechanisms driving inter-individual variation in response to childhood severe malnutrition, and how it impacts recovery and eventually life in the long-term. To address this, we will use systems biology approaches, i.e. integration of metabolomics, lipidomics, proteomics, genomics, using both pre-clinical and epidemiological/clinical studies.

A. Metabolic regulation during severe malnutrition

Malnutrition causes severe metabolic perturbation, and children react differently to these insults. In its severe form, malnutrition is often categorized as marasmus (or severe wasting), characterized by extreme muscle wasting, or kwashiorkor (oedematous malnutrition), characterized by oedema, skin and hair changes and fatty liver. The aetiology of these divergent phenotypes remains elusive. Furthermore, the impact of malnutrition on other life functions, such as immunity and reproduction, remains to be fully elucidated. Our group is studying the metabolic consequences of malnutrition in clinical settings (Kenya, Malawi, Niger, Philippines, etc) and in animal and in vitro models of undernutrition.

B. Long-term consequences of malnutrition

As economies improve in low and middle-income countries, access to high caloric “Western” diets increases among those who were previously malnourished during childhood – the so called: Double Burden of Malnutrition. Children who were previously malnourished are at a higher risk of developing cardio-metabolic non-communicable diseases during adulthood. The mechanisms driving these poor long-term outcomes are not fully understood. Using systems biology approaches applied to both epidemiological and pre-clinical mechanistic studies, our group is investigating the main metabolic pathways involved in driving these health consequences among survivors of severe malnutrition.

C. Improved rehabilitation strategies based on systems information

Using the knowledge obtained from above, our group is developing nutritional intervention strategies that address specific metabolic needs of children with severe malnutrition which aim to (1) improve clinical outcomes (i.e. reduce mortality during hospitalization, improve bioavailability of nutrients), (2) promote growth and development following malnutrition, and (3) reduce risk of non-communicable disease later in life.