Högskolan i Skövde

Overlap of irritable bowel syndrome (IBS) with gastroduodenal disorders of gut–brain interaction (DGBI) is common and associated with more severe symptoms, but the underlying causes of these severe symptoms are unknown. Here, neuropeptide signalling, neuronal plasticity, and compartment-specific nerve architecture in the colonic mucosa were examined in this phenotype. Colonic samples from healthy controls (HC, n=8) and IBS patients with or without gastroduodenal DGBI overlap (n=16 for each group) were examined for vasoactive intestinal polypeptide (VIP) and growth-associated protein-43 (GAP43) mRNA and protein expression. VIP and GAP43 were quantified by immunohistochemistry in the crypt, lamina propria, mucosa, and muscularis mucosa.These data were integrated with rectal barostat measurements of visceral sensitivity and with self-rating of anxiety, depression, and abdominal pain, using validated questionnaires. Non-parametric correlations and comparative statistics were used to analyse differences between groups, transcription–protein coupling, and associations with symptoms. IBS patients with DGBI overlap had higher VIP and GAP43 mRNA, but not protein, expression. For each protein, expression intensity correlated closely between mucosal layers in IBS participants but not in GAP43 in HC, whereas correlations with mRNA levels and symptoms were compartment-specific. Distinct, compartment-specific correlations between markers were observed in IBS with vs. without overlapping gastroduodenal DGBI. Lamina propria and mucosal GAP43 expression correlated inversely with abdominal pain in participants with IBS, which was largely driven by individuals with overlapping DGBI. Neuronal remodelling is differentially associated with abdominal pain and spatial neuronal distribution in the colonic mucosa in people with IBS with vs. without concomitant gastroduodenal DGBI.