OC-035 Mechanism of Lactose Intolerance in Irritable Bowel Syndrome: Role of Anxiety, Mucosal Immunity and Visceral Hypersensitivity

Abstract

INTRODUCTION: Many patients with Irritable Bowel Syndrome (IBS) consider that certain foods trigger bloating, diarrhea and other digestive symptoms; however the mechanism underlying “food intolerance” is unknown. AIMS&METHODS: We assessed the role of psychology, mucosal immunity and visceral sensitivity on the development of lactose intolerance (LI) in IBS patients and healthy controls (HCs) with lactase deficiency. IBS-D patients meeting Rome III criteria (n=277) and matched HCs (n=64) underwent a 20g lactose hydrogen breath test (LHBT): a validated model of food intolerance (Yang Clin Gastro Hep 2013). Hospital Anxiety and Depression Score was obtained. Hydrogen (H2) gas production was measured by breath test. LI symptoms (bloating, borborygmi, nausea, pain and diarrhea) were recorded using a Lickert scale. An increase in symptom score of >1 on a scale of 0-4 defined LI. Rectal sensitivity was measured by barostat with normal values defined by HCs. Additionally, 55 IBS-D patients and 18 HCs underwent ileo-colonoscopy with biopsies obtained from colon and terminal ileum (TI) to quantify mast cells (MCs), T-cells, and enterochromaffin cells (ECC). RESULTS: H2 production was similar in both groups; but LI was more frequent in IBS than HCs (54% vs. 28%, P<0.001) as were individual symptoms including bloating (39% vs. 14%, P<0.001), borborygmi (39% vs. 22%, P=0.010), pain (31% vs. 11%, P = 0.001) and diarrhea (29% vs. 9%, P=0.001). IBS patients with LI were more anxious (p<0.045) and had higher rectal sensitivity (P=0.001) than patients without LI and controls. Multivariate analysis indicated that H2 production in the upper quartile (OR2.2 (95%CI 1.1-4.4), P=0.028) and the presence of visceral hypersensitivity (OR6.6 (1.7-25.0), P=0.005) were associated with total symptom score. In those that underwent colonoscopy, IBS patients with LI had increased MCs (p<0.006), T-cells and ECC (both p<0.05) in colonic and TI mucosa compared to IBS patients without LI and HCs. Multivariate analysis indicated that total symptom score was associated with anxiety, mucosal inflammation and hypersensitivity (all r>0.5 and P<0.001). CONCLUSION: Gas production and hypersensitivity to luminal distension both contribute to digestive symptoms after lactose ingestion. IBS-D patients with LI are characterized by anxiety, evidence of mucosal inflammation and visceral hypersensitivity. These results provide insight into the mechanism of food intolerance. The presence of these biomarkers may identify a subgroup of IBS patients likely to respond to dietary management.