Intestinal chemosensitivity in irritable bowel syndrome associates with small intestinal TRPV channel expression. Issue 9 (2nd September 2021)

• Record Type: Journal Article
• Authors: Grover, Madhusudan; Berumen, Antonio; Peters, Stephanie; Wei, Ting; Breen‐Lyles, Margaret; Harmsen, William S.; Busciglio, Irene; Burton, Duane; Vazquez Roque, Maria; DeVault, Kenneth R.; Camilleri, Michael; Wallace, Michael; Dasari, Surendra; Neumann, Helmut; Houghton, Lesley A.
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 54:Issue 9(2021)
• Page Start: 1179
• Page End: 1192
• Publication Date: 2021-09-02
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.16591
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: 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. Abstract : Irritable bowel syndrome (IBS) patients experienced greater symptoms during small bowel lipid infusion. In vivo small intestinal permeability and small bowel mucosal architecture was similar between IBS patients and healthy volunteers. However, the small intestinal expression of TRPV channels was increased in IBS which associated with lipid‐induced symptoms and rectal hypersensitivity in these patients.