Thapaliya, Gita
(2019)
Altered appetite in Crohn’s Disease: deconstructing the
enteroendocrine axis using fMRI.
PhD thesis, University of Nottingham.
Abstract
Reduced appetite has been observed in patients with ileal Crohn’s disease, which has been attributed to the upregulation of enteroendocrine cells and the consequent increase of satiety hormones secretion, therefore possibly negatively affecting appetite signalling to the central nervous system. The specific hypotheses to be tested in this thesis were that Crohn’s disease patients with ileal inflammation, when compared with Crohn’s disease patients with colonic inflammation and healthy controls, will show A) an alteration in brain-gut stimulation, B) an increase in the postprandial plasma enteroendocrine peptides response (CCK, GLP-1 and PYY) with associated alteration in appetite scores, C) a change in eating behaviour, and D) an alteration in brain structure and resting-state functional connectivity.
Ileal Crohn’s disease patients showed greater fasting GLP-1 concentrations compared with healthy controls. No difference was found between ileal and colonic Crohn’s disease patients in the fasting and postprandial concentrations of GLP-1, CCK and PYY. The ileal Crohn’s disease patients showed a greater postprandial decrease in neuronal activity in the right superior frontal gyrus in the default mode network in response to saline compared with the fat meal. The mechanism underlying this phenomenon is unclear and requires further investigation. Greater neuronal activity was found in areas including the cerebellum, hippocampus, posterior cingulate gyrus, middle temporal gyrus, thalamus and medulla in response to fat, which is in line with the previous literature. The fat induced greater activity of the posterior cingulate gyrus, was driven by Crohn’s disease patients, with colonic Crohn’s disease patients showing stronger activation in this region compared with the ileal Crohn’s disease patients. This finding may be linked with abdominal pain or GLP-1 elevations, which remains to be investigated. Stronger hedonic control of food intake was observed in the ileal CD patients compared with healthy controls, based on their explicit wanting/liking appeal bias for high-fat foods, however, this was not translated into actual increased calorie intake, perhaps because of fear of triggering or worsening symptoms. Ileal CD patients also exhibited greater impulsivity compared with colonic CD patients. These findings indicate that eating behaviour in ileal Crohn’s disease patients is likely to be impulse and reward-driven to alleviate symptoms such as low mood, abdominal pain and chronic fatigue. Therefore, a complex interplay of gut peptides, psychological factors, disease related symptoms, inflammatory burden may ultimately guide eating behaviour in ileal CD patients.
Grey matter and white matter volume atrophy and cortical thinning were found in active Crohn’s disease patients in regions such as the precentral gyrus (motor cortex) and the postcentral gyrus. The relative atrophy of the motor cortex could be a possible central cause of fatigue in Crohn’s disease patients. Alterations were found in the resting-state functional connectivity between Crohn’s disease patients and healthy controls in the networks implicated in cognition, attention, emotion and pain. These findings may reflect neuroplasticity effects in response to chronic inflammation and disease symptoms such as abdominal pain and fatigue.
This work was carried out between June 2015 and September 2019 at the National Institute of Health Research,Nottingham Biomedical Research Centre at the Queens Medical Centre Campus and the Sir Peter Mansfield Imaging Centre Nottingham.All work described in this thesis was performed by the author, except where indicated.
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