title: A combined nutrient and lactulose challenge test allows symptom-based clustering of patients with irritable bowel syndrome.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Digestive Health, Danone Research, Palaiseau, France. boris.le-neve@danone.com
authors.forename: B
authors.initials: B
authors.lastname: Le Nevé
authors.forename: I
authors.initials: I
authors.lastname: Posserud
authors.forename: L
authors.initials: L
authors.lastname: Böhn
authors.forename: D
authors.initials: D
authors.lastname: Guyonnet
authors.forename: P
authors.initials: P
authors.lastname: Rondeau
authors.forename: K
authors.initials: K
authors.lastname: Tillisch
authors.forename: B
authors.initials: B
authors.lastname: Naliboff
authors.forename: E A
authors.initials: EA
authors.lastname: Mayer
authors.forename: M
authors.initials: M
authors.lastname: Simrén
mesh_terms: D015746:Abdominal Pain / Q000209:etiology; D000328:Adult; D000368:Aged; D001007:Anxiety / Q000175:diagnosis; D001944:Breath Tests; D016000:Cluster Analysis; D018592:Cross-Over Studies; D003863:Depression / Q000175:diagnosis; D004311:Double-Blind Method; D005260:Female; D005414:Flatulence / Q000209:etiology; D005526:Food, Formulated; D005765:Gastrointestinal Agents / Q000008:administration & dosage; D005767:Gastrointestinal Diseases / Q000150:complications / Q000503:physiopathology; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000503:physiopathology* / Q000523:psychology; D007792:Lactulose / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019518:Postprandial Period; D011237:Predictive Value of Tests; D012720:Severity of Illness Index
chemical_list: D005765:Gastrointestinal Agents; D007792:Lactulose