Severe acute malnutrition (SAM) is the overall leading cause of childhood mortality worldwide,

either directly or indirectly. SAM is categorized into either marasmus or kwashiorkor, the latter

being characterized by additional clinical features like oedema and fatty liver. It however remains

unclear what causes these additional factors and their higher mortality rates compared to

marasmus. Several hypotheses have been proposed but none have substantially established

causality.

This proposal aims to explore the role of farnesoid X receptor (FXR) activity on the onset of

kwashiorkor from bench to bedside. Thus, the project is composed of 2 work packages (WP). In

WP1, the role of FXR activity in the aetiology of kwashiorkor will be explored using FXR-knockout

mouse models. Clinical and biochemical parameters will be checked and compared to those

reported in children with kwashiorkor. In WP2, blood, feces and urine will be collected from

kwashiorkor and marasmus patients at different severity levels in DR Congo. Levels of bile acid and

other FXR-related metabolites will be compared with each other and with non-malnourished

controls. Moreover, metabolomics will be used to find other biomarkers, which could aid in

understanding the causes of the disease.

In this project, the main hypothesis is that kwashiorkor patients have lost their ability to activate

FXR and hence develop more serious complications than marasmus.