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A Combined Nutrient and Lactulose Challenge Test Allows Symptom-Based Clustering of Patients With Irritable Bowel Syndrome

Le Nevé, B PhD1; Posserud, I MD2; Böhn, L PhD2; Guyonnet, D PhD1; Rondeau, P PhD4; Tillisch, K MD3; Naliboff, B PhD3; Mayer, E A MD3; Simrén, M MD2

American Journal of Gastroenterology: May 2013 - Volume 108 - Issue 5 - p 786–795
doi: 10.1038/ajg.2013.75
Functional GI Disorders

OBJECTIVES: The aim of the present pilot study was to evaluate the usefulness of a test meal containing lactulose in the non-invasive assessment of visceral sensitivity in irritable bowel syndrome (IBS), and to identify subsets of IBS patients based on gastrointestinal (GI) symptom generation.

METHODS: We included 43 patients with IBS (Rome III) and 29 healthy controls. The fasted subjects were served three test meals consisting of a 400-ml liquid breakfast alone or containing lactulose (15 or 25 g) in a double-blind crossover design. Seven GI symptoms, overall digestive comfort, and exhaled H2/CH4 were assessed at baseline and every 15 min during 4 h after meal intake. Anxiety and depression were assessed only at baseline. A mapping of the seven GI symptoms was done using a Principal Component Analysis (4 h mean area under the curve, AUC). Independently, a hierarchical cluster analysis was performed on the same parameters to identify GI symptom-based IBS clusters.

RESULTS: All three tests were well tolerated. The 25 g lactulose challenge enabled discrimination of IBS from healthy controls according to the symptom response. This challenge also enabled clustering of IBS subjects in two subgroups based mainly on bloating, distension, and discomfort symptoms (2,457 (2,043–2,872), 2,450 (1,910–2,990), 2,602 (2,126–3,079) vs. 537 (383–691), 619 (458–780), 643 (432–854); 4 h mean AUC;P<0.0001), overall digestive comfort (1807 (1318–2295) vs. 3350 (2942–3758); 4 h mean AUC;P<0.0001), and anxiety at baseline (9.2 (7.0–11.5) vs. 5.5 (4.2–6.9); Hospital Anxiety and Depression scale anxiety mean scores;P=0.003). This clustering was independent of the Rome III subtype and the amount of exhaled H2/CH4.

CONCLUSIONS: The lactulose challenge test seems to be a promising tool to assess visceral sensitivity in IBS, and to subgroup IBS patients based on their symptom pattern.

1 Department of Digestive Health, Danone Research, Palaiseau, France

2 Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

3 Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, Departments of Medicine, Physiology and Psychiatry, David Geffen School of Medicine at University of California, Los Angeles, California, USA

4 Department of Biostatistics, Danone Research, Palaiseau, France

Correspondence: Le Nevé, Department of Digestive Health, Danone Research, Route Départementale 128, 91767 Palaiseau, France. E-mail:

Received 14 December 2012; accepted 26 February 2013

published online 16 April 2013

© The American College of Gastroenterology 2013. All Rights Reserved.
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