Intestinal chemosensitivity in irritable bowel syndrome associates with small intestinal TRPV channel expression

BACKGROUND Irritable bowel syndrome (IBS) patients often experience meal-associated symptoms. However, the underlying mechanisms are unclear. AIM To determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS METHODS: We recruited 26 IBS patients (12 IBS-C, 14 IBS-D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed using a barostat before and after small bowel lipid infusion; symptoms were assessed throughout. Next, an extended upper endoscopy with probe-based confocal laser endomicroscopy (pCLE) was performed with changes induced by lipids. Duodenal and jejunal mucosal biopsies were obtained for transcriptomics. RESULTS Following lipid infusion, a higher proportion of HV than IBS patients reported no pain, no nausea, no fullness and no urgency (P < 0.05 for all). In a model adjusted for sex and anxiety, IBS-C and IBS-D patients had lower thresholds for first rectal sensation (P = 0.0007) and pain (P = 0.004) than HV. In vivo small intestinal permeability and mean pCLE scores were similar between IBS patients and HV. Post-lipid, pCLE scores were higher than pre-lipid but were not different between groups. Baseline duodenal transient receptor potential vanilloid (TRPV) 1 and 3 expression was increased in IBS-D, and TRPV3 in IBS-C. Duodenal TRPV1 expression correlated with abdominal pain (r = 0.51, FDR = 0.01), and inversely with first rectal sensation (r = -0.48, FDR = 0.01) and pain (r = -0.41, FDR = 0.02) thresholds. CONCLUSION Lipid infusion elicits a greater symptom response in IBS patients than HV, which is associated with small intestinal expression of TRPV channels. TRPV-mediated small intestinal chemosensitivity may mediate post-meal symptoms in IBS.