title: Colon Hypersensitivity to Distension, Rather Than Excessive Gas Production, Produces Carbohydrate-Related Symptoms in Individuals With Irritable Bowel Syndrome.
abstract: Poorly digested, fermentable carbohydrates may induce symptoms of irritable bowel syndrome (IBS) via unclear mechanisms. We performed a randomized trial with magnetic resonance imaging (MRI) analysis to investigate correlations between symptoms and changes in small- and large-bowel contents after oral challenge.
  
  
  
  We performed a 3-period, cross-over study of 29 adult patients with IBS (based on Rome III criteria, with symptoms of abdominal pain or discomfort for at least 2 days/wk) and reported bloating. In parallel, we performed the same study of 29 healthy individuals (controls). Studies were performed in the United Kingdom from January 2013 through February 2015. On 3 separate occasions (at least 7 days apart), subjects were given a 500-mL drink containing 40 g of carbohydrate (glucose in the first period, fructose in the second, and inulin in the third, in a random order). Levels of breath hydrogen were measured and intestinal content was assessed by MRI before and at various time points after consumption of each drink. Symptoms were determined based on subjects' responses to the Hospital Anxiety and Depression Scale questionnaire and the Patient Health Questionnaire-15. The primary end point was whether participants had a clinically important symptom response during the 300 minutes after consumption of the drink.
  
  
  
  More patients with IBS reached the predefined symptom threshold after intake of inulin (13 of 29) or fructose (11 of 29) than glucose (6 of 29). Symptoms peaked sooner after intake of fructose than inulin. Fructose increased small-bowel water content in both patients and controls whereas inulin increased colonic volume and gas in both. Fructose and inulin increased breath hydrogen levels in both groups, compared with glucose; fructose produced an earlier increase than inulin. Controls had lower symptom scores during the period after drink consumption than patients with IBS, despite similar MRI parameters and breath hydrogen responses. In patients who reached the symptom threshold after inulin intake, peak symptom intensity correlated with peak colonic gas (r = 0.57; P < .05). Changes in MRI features and peak breath hydrogen levels were similar in patients who did and did not reach the symptom threshold.
  
  
  
  Patients with IBS and healthy individuals without IBS (controls) have similar physiological responses after intake of fructose or inulin; patients reported symptoms more frequently after inulin than controls. In patients with a response to inulin, symptoms related to levels of intraluminal gas, but peak gas levels did not differ significantly between responders, nonresponders, or controls. This indicates that colonic hypersensitivity to distension, rather than excessive gas production, produces carbohydrate-related symptoms in patients with IBS. Clinicaltrials.gov no: NCT01776853.
authors.affiliation: Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Giles
authors.initials: G
authors.lastname: Major
authors.affiliation: Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Sue
authors.initials: S
authors.lastname: Pritchard
authors.affiliation: Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Murray
authors.affiliation: Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Alappadan
authors.affiliation: Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Hoad
authors.affiliation: Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Luca
authors.initials: L
authors.lastname: Marciani
authors.affiliation: Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Penny
authors.initials: P
authors.lastname: Gowland
authors.affiliation: Nottingham Digestive Diseases Centre, University of Nottingham, Nottingham, United Kingdom. Electronic address: robin.spiller@nottingham.ac.uk.
authors.forename: Robin
authors.initials: R
authors.lastname: Spiller
mesh_terms: D015746:Abdominal Pain / Q000209:etiology; D000328:Adult; D019540:Area Under Curve; D001944:Breath Tests; D016022:Case-Control Studies; D003106:Colon / Q000503:physiopathology*; D012809:Colon, Sigmoid / Q000000981:diagnostic imaging; D018592:Cross-Over Studies; D003967:Diarrhea / Q000209:etiology; D004040:Dietary Carbohydrates / Q000378:metabolism* / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005414:Flatulence / Q000209:etiology; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology; D005766:Gastrointestinal Contents / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006859:Hydrogen / Q000032:analysis / Q000378:metabolism*; D007444:Inulin / Q000378:metabolism / Q000494:pharmacology; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D004040:Dietary Carbohydrates; D005632:Fructose; D006859:Hydrogen; D007444:Inulin; D005947:Glucose
keywords: Bloating; FODMAP; Fermentation; MRI