999 A Combined Nutrient and Lactulose Challenge Test Allows Symptom-Based Clustering of Patients With Irritable Bowel Syndrome Unrelated to Exhaled Gas and ROME III Subtype

Background: Postprandial worsening of symptoms is common in patients with irritable bowel syndrome (IBS), and alterations in the gut microbiota may be involved in IBS symptom generation. Lactulose is a non-digestible carbohydrate fermented by gut bacteria, which might serve as a tool to study bacterial involvement in postprandial symptom generation. Aim: To evaluate the usefulness of a test meal containing lactulose in the assessment of gastrointestinal (GI) symptom generation in IBS. Methods: We included 43 patients with IBS (Rome III) and 29 healthy controls. The fasted subjects were served each of the three test meals consisting in a 400ml liquid breakfast (Nutridrink®, 1.5 kcal/ml) containing lactulose (15g or 25g) or no additive (nutrient only) at least one week apart in a doubleblind randomized protocol. The severity of GI symptoms, anxiety and depression were evaluated by questionnaire before the test, and seven GI symptoms, the overall level of digestive comfort and the amount of exhaled H2/CH4 were assessed every 15min during 4hrs after meal intake. A 4h mean AUC for individual symptoms and a Principal Components Analysis (PCA) on all symptoms followed by cluster analysis were performed in IBS patients. Results: All three test meals were well tolerated by all subjects. IBS subjects showed significantly higher scores than controls on all symptoms for the three test meals. No correlation was found between amount of exhaled gas and severity of symptoms. PCA showed a strong negative correlation between overall digestive comfort and bloating, discomfort and distension, the most representative symptoms induced by the challenge. The 25g dose induced the highest scores in IBS for bloating, discomfort and distension (8.7±4.8, 10.0±5.3, 9.7±5.4) but did not differ significantly from the 15g dose (7.8±4.6, 8.3±5.3, 8.7±5.3). A 25g lactulose challenge allowed clustering of IBS subjects in two separated subgroups based on their symptom response. Patients in the High GI symptom group (n=16; 13.2±3.3, 14.4±3.2, 14.2±3.3) displayed higher levels of general anxiety (9.2±4.3 vs. 5.5±3.4; p<0.003) and GI symptom-specific anxiety (42.5±19.6 vs 30.1±17.0; p<0.03) and lower overall digestive comfort (11.0±4.2 vs 16.8±3.1; p<0.0001) than patients in the Low GI symptom group (n=26; 5.6±3.1, 7.3±4.4, 5.8±4.5; p<0.0001). This clustering was independent of the Rome III subtype classification and the amount of exhaled H2/CH4. Conclusion: A test meal containing 25 g of lactulose discriminates IBS patients from healthy controls, and allows clustering of IBS subjects according to their symptom response, independent of Rome III subtypes or the amount of exhaled gas. The lactulose challenge test may be a promising tool to better define postprandial symptoms in IBS and to evaluate the efficacy of new treatment options.