PROTEIN NUTRITION IN PAEDIATRIC CROHN’S DISEASE

Abstract

Altered nutritional status is well documented in Crohn’s disease patients, which may lead to low muscle mass and deteriorated function (sarcopenia) and adverse disease outcomes. Although a variety of experimental methods have assessed muscle mass and function in paediatric CD patients, there is no conclusive consensus on the definition of sarcopenia in those patients. However, most of the studies in the literature have showed reduction in muscle mass (MM), lean mass (LM) and fat-free mass (FFM) in paediatric CD compared with healthy controls or reference data. Historically, underweight was frequently linked with paediatric CD. However, recent evidence suggests a shift towards adiposity rather than underweight being prevalent in paediatric CD. Our knowledge of the relationship between adiposity and adverse disease outcomes in children with CD is limited. In addition, clinical characteristics of CD patients may vary depending on age at diagnosis. Moreover, adult CD patients exhibit altered nutritional status and eating behaviour that impact negatively on habitual dietary protein intake, protein metabolism and muscle mass. However, these relationships have never been investigated in paediatric CD. This PhD thesis used the gold standard technique, magnetic resonance imaging (MRI), to assess leg muscle volume in children with stable CD disease and compared it with matched healthy subjects. These findings were linked with dietary protein intake, fasting plasma amino acids (AAs) and eating behaviour traits. In addition, the MRI technique was used to compare psoas muscle cross sectional area (PCSA) between paediatric with active CD versus those with inactive CD. However, conclusive findings were limited due to small sample size in both studies. This thesis highlighted the need for standardisation of body composition and sarcopenia terminology, as well as the valid use of assessment tools in adequately powered populations with appropriately matched comparators, to establish a clear definition of sarcopenia and assess its prevalence in paediatric IBD. In addition, it revealed that adiposity is linked to poor clinical outcomes in a long-term follow-up cohort of paediatric-onset CD, and that the age at disease onset is also associated with negative clinical outcomes. Moreover, this thesis revealed comparable dietary protein and energy intake, and eating behaviour traits between stable CD paediatric patients and matched healthy controls, which may explain the lack of differences in leg muscle volume and handgrip strength (indices of sarcopenia) and circulating AAs between groups. Furthermore, there were no significant differences in PCSA assessed by MRI between active and inactive paediatric CD; however, age and gender were associated with muscle mass. These findings might have been affected by disease duration and further disease burden that need to be taken into consideration in future studies. Data collection in this thesis was significantly impacted by the COVID pandemic. Hence, most of the studies performed were either retrospective in nature or cross-sectional studies which require further prospective cohort studies with larger sample size to enhance generalisability and confirm findings. Therefore, the aims of this thesis were to a) systematically evaluate changes in skeletal muscle mass and function in paediatric IBD, b) investigate the relationship between adiposity and age of disease onset with adverse clinical outcomes in paediatric patients with CD, c) assess protein intake, circulating AAs and skeletal muscle mass and evaluate eating behaviour in paediatric CD and age, sex and BMI-matched healthy controls and d) describe the differences in PCSA assessed by MRI between active and inactive paediatric CD and examine the impact of age, gender, disease activity, and other disease-related variables on muscle mass. This research integrated several approaches to assess the impact of nutritional status, early age of disease onset on disease outcomes, and muscle size in paediatric CD patients. In addition, it compared protein intake, eating behaviour between children with stable CD and healthy matched peers to offer a holistic understanding of their impact on muscle mass and strength (as an index of sarcopenia) and circulating amino acids profiles in paediatric CD. While the studies presented in this thesis did not reveal significant differences in certain aspects of dietary protein intake, muscle size and strength, they did highlight several areas requiring further investigation. The complicated nature of disease burden and activity, alongside paediatric growth, necessitates further research to better understand the definition, management and prevention of sarcopenia in paediatric CD patients.