Altered appetite in Crohn's disease: The role of the enteroendocrine axis (BROAD)
1st December 2014 - ongoing
Status: In Recruitment
Specialism: Lower GI.
Team: Dr Gordon Moran.
Crohn’s disease (CD) is a pan-enteric intestinal inflammatory disorder that may commonly present with nutritional problems. Up to 75% of hospitalised CD patients are malnourished and as many as 50% are in negative nitrogen balance1. Apart from the disease burden and repeated surgery, reduced appetite2 and associated symptoms such as nausea might be possible aetiological factors to this problem. Malnutrition worsens patient-related outcomes and decreases quality of life3.
Enteroendocrine cells (EC) are gut-related nutrient sensors that relay to the central nervous system (CNS) to control food intake. In CD, we have shown an upregulation of EC peptides at the tissue and plasma level with changes significantly correlating to appetite-related scores2, 4. We hypothesize that an increase in EC expression might affect appetite regulation through an increase in CNS signalling.
Magnetic resonance imaging (MRI) techniques now enable us to map changes in CNS signalling through blood-oxygen-level-dependent (BOLD) effect. This is a surrogate marker of CNS activity as it indicates a shift from oxy- to deoxyhaemoglobin secondary to neuronal activity. Fatty-acids, (e.g. dodecanoate) lead to EC-dependent increase in BOLD effect in the brainstem, the pons, hypothalamus, cerebellum and the motor cortical areas.
We aim to study appetite regulation in a cohort of CD patients with inflammatory uncomplicated small bowel disease. We plan to a) coherently quantify abnormalities in appetite using appetite-related questionnaires and an ad libitum test meal, b) deconstruct the EC pathway using magnetic resonance imaging (MRI) to quantify the CNS response to a fatty acid test, c) correlate these findings to postprandial plasma EC peptide levels d) correlate our clinical findings to quality of life outcomes.
Until now, loss of appetite, weight loss and the ascribed poor quality of life has always been indirectly targeted by anti-inflammatory or immunosuppressive medication and nutrient supplementation. Findings from this proposed work would serve as a platform for more translational work bringing to the fore EC peptide inhibitors as appetite modulating agents in the treatment of CD.
|Altered Appetite in Crohn’s disease: Deconstructing the enteroendocrine axis using fMRI.||£140,508.32|