Effect of Diet on Intestinal Gas Production and Evacuation in Healthy Subjects and Flatulent Patients
Condition: Flatulence
MeSH terms: Flatulence
Study type: Interventional

Summary: 
      Background Some patients complain of excessive evacuation, which may become socially
      disabling (Azpiroz F & Malagelada J-R, 2005). However, there no systematic investigation on
      the range of gas evacuation in healthy subjects and in subjects complaining of flatulence
      under basal conditions and in response to a high-flatulogenic diet (Azpiroz F & Levitt DG,
      2009).

      Hypothesis Patients complaining of excessive passage of gas per anus have more intestinal gas
      production and more anal gas evacuation during basal conditions and in response to a high
      flatulogenic diet than healthy subjects. This abnormality is related to the differences in
      colonic microflora.

      Objectives

        -  To determine the normal range of intestinal gas evacuation under basal conditions and in
           response to a high flatulogenic diet.

        -  In patients complaining of flatulence, to determine whether intestinal gas evacuation
           under basal conditions and in response to a high flatulogenic diet is increased.

        -  To identify differences in the microbiota pattern in subjects with normal and excessive
           anal gas evacuation.

        -  In patients complaining of flatulence, to determine the segmental distribution of
           intestinal gas after a diet challenge.

      Methods Healthy subjects (n=20) and patients complaining of flatulence (n=30) will undergo a
      3-day basal phase on their current diet and a 3-day challenge phase on a high-flatulogenic
      diet; patients will be followed-up for 7 days on a low-flatulogenic diet. The following g
      measurements will be performed: daily measurement of the number of anal gas passages with an
      event marker, continuous recording of anal gas evacuation in the laboratory using an
      electronic leakage-free gas collection system, colonic flora analysis by fecal sampling, and
      segmental gas distribution in the gut by abdominal computer tomography (CT) imaging.

      Relevance These studies will allow to develop the normal range of anal gas evacuation during
      basal conditions. Furthermore, a provocative test will be developed for the diagnosis of
      excessive gas production in patients complaining of flatulence. This data will allow a proper
      diagnosis of these patients and will pave the path for a rational management and for the
      development of evidence-based treatment strategies. This pilot study will allow a proper
      design with adequate sample size calculation in future interventional studies.
    

Detailed description: 
      Background Some patients complain of excessive evacuation, which may become socially
      disabling (Azpiroz F & Malagelada J-R, 2005). However, the physiology and pathophysiology of
      flatulence remains poorly understood (Azpiroz F & Levitt DG, 2009).

      Gas evacuated by anus originates by-and-large in the colon, where unabsorbed meal residues
      are fermented by colonic bacteria (Anderson et al., 1981;Levitt et al., 1987;Flourie et al.,
      1988). Indeed, it has been shown that some food components are incompletely absorbed in the
      small bowel and enter the colon (Wolever & Robb, 1992;Grimble, 1989;Steggerda FR, 1968;Wagner
      et al., 1977;Steggerda F.R. & Dimmick, 1966;Stone-Dorshow & Levitt, 1987;Wursch et al., 1989)
      and that other intraluminal substrates interfere with the absorption of nutrients (Boibin M
      et al., 1998;Hamberg et al., 1989;Brugge & Rosenfeld, 1987;Taylor et al., 1986;Layer et al.,
      1986). Hence, the volume of gas production and anal evacuation is determined by two main
      factors: the diet, particularly the amount of fermentable residues, and the individual
      composition of colonic microflora. Within subjects, gas output varies in relation to the diet
      (Steggerda FR, 1968;Kirk, 1949). However, there is a great interindividual variability, and
      gas evacuation in subjects maintained on a similar diet may differ substantially.

      It has been shown that healthy subjects on a normal diet containing 200 g of beans evacuate
      705 mL gas per 24 hours, whereas with a fiber the diet gas evacuation was 214 mL (Tomlin et
      al., 1991). In healthy subjects the frequency of gas evacuation is variable, usually around
      10 evacuation per day (Furne & Levitt, 1996). Based on observations on a patient that who
      passed large amounts of flatus, a classification of foodstuffs depending on their gas
      producing capacity was elaborated (Sutalf LO & Levitt MD, 1979). Few studies on specific
      foodstuffs have been later added to complement this information (Wolever & Robb, 1992;Wagner
      et al., 1977;Hickey C et al., 1972). However, there no systematic investigation on the range
      of gas evacuation in healthy subjects and in subjects complaining of flatulence under basal
      conditions and in response to a high-flatulogenic diet.

      Procedures Recruitment questionnaire A questionnaire will be used to evaluate gas evacuation,
      bowel habit and functional gut symptoms.

      Daily measurement of the number of anal gas evacuations and symptoms The number of gas
      evacuations per anus will be measured using an event marker during daytime. At the end of the
      day the following parameters will be recorded on a questionnaire: discomfort related to
      flatulence and evaluation of abdominal discomfort/pain (using 0-10 analogue scales); the
      number of bowel movements and form (using the Bristol scale; (Heaton & O'Donnell, 1994) and
      gastrointestinal well-being (satisfaction/dissatisfaction using a 10 point scale graded from
      +5 to -5).

      Analysis of colonic flora The composition of the intestinal flora will be evaluated measuring
      flora composition in stools. Subjects will be supplied with two Stool Collecting Kits (each
      containing two weighed sampling tubes containing RNA synthesis stabilization buffers (RNA
      later, Ambion), one of which is a spare) into which they will provide a small sample of their
      stool (at least 30g). After mixing the stool with the buffer in the supplied tube, subjects
      will store the tubes in the box at home until they next visit at the hospital, where it will
      be centrifuged at 12000rpm for 5 minutes, supernatant removed and fecal pellet stored at -
      80oC in the Gastroenterology Research Unit. Samples will be transported to Danone Research,
      France where they will be analysed for composition of intestinal flora (bacteria).

      Using molecular based methods, the concentration of dominant and some sub-dominant bacterial
      groups of intestinal flora will be measured. These include bacteria that belong to
      Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria, Euryarcheota groups.

      Continuous recording of anal gas evacuation Participants will be studied in the laboratory.
      After a standard breakfast, rectal gas will be collected via a rectal cannula. Anal gas will
      be collected via a leak proof, low resistance collection line, using a barostat and the
      volume will be continuously recorded for either 3 or 8 hours (see study design). The
      composition of the gas collected will be analyzed.

      Once the subjects are positioned in bed, a non-stretch belt, 48 mm wide, with a metric scale
      will be adjusted around the abdomen by means of two elastic bands. All girth changes will be
      measured while the subjects are breathing relaxed, and will be referenced to the mid point of
      respiratory displacements.

      A graded questionnaire will be used to measure the intensity and the type of sensations
      perceived, and an anatomical questionnaire to measure the location and extension of the
      perceived sensations. The graded questionnaire includes five visual analogue scales graded
      from 0 (no perception) to 6 (pain), specifically for scoring: a) sensation of increased
      abdominal pressure, b) sensation of abdominal distension, c) colicky/rumbling sensation, d)
      puncture/stinging sensation, and d) other type of sensation (to be specified by the
      participant in the questionnaire), respectively. The questionnaire includes two additional
      scales for scoring feeling of difficult evacuation of gas per anus, and belching,
      respectively, that will be analyzed separately. Subjects will be asked to score any perceived
      sensation (one or more perceived simultaneously) on the scales. The anatomical questionnaire
      incorporates a diagram of the abdomen divided in nine regions corresponding to epigastrium,
      periumbilical area, hypogastrium, both hypochondria, flanks, and ileal fossae. Subjects will
      be instructed to mark the location, i.e., abdominal region (s) or extraabdominal, where the
      sensations are perceived.

      Segmental gas distribution in the gut In patients complaining of bloating, an abdominal CT
      scan will be taken. This scan will be used to rule out organic disorders. Furthermore, using
      an original program, abdominal morpho-volumetric analysis will be performed to measure gas
      volumes in different gut. All female participants with childbearing potential will undergo a
      urine pregnancy test 24 hours prior to the scan.

      Hyperflatulogenic diet challenge For 3 days participants will be asked to consume a diet rich
      in fermentable residues to increase their gas production rate.

      Low-flatulogenic diet At the end of the study, patients will be put on a low residue diet for
      7 days; this will give an indication of the potentially expected response to treatment.

      Working Plan Each subject will attend the following visits; the first recruitment visit will
      be performed by the attending physician in the outpatient clinic, and the rest, including the
      physiological measurements in the Digestive System Research Unit; CT imaging will be
      performed in the Department of Radiology.

      Visit 1. Recruitment: entry questionnaires. Visit 2. Before basal period: instructions,
      informed consent, and delivery of event marker, questionnaires, and material for fecal
      sampling.

      Visit 3. Last day of basal phase. Continuous recording of anal gas evacuation. Delivery of
      dietary instructions (high-flatulogenic diet) and questionnaires. In 8 patients segmental gas
      distribution will be also measured during the basal phase.

      Visit 4. Last day of challenge phase. Continuous recording of anal gas evacuation. CT for
      evaluation of segmental gas distribution in the gut. In patients only: delivery of dietary
      instructions (low-flatulogenic diet) and questionnaires.

      Visit 5. Last day of correction phase. In patients only: collection of data and materials.
    

Intervention name(s): High flatulogenic diet
Intervention type(s): Dietary Supplement
Intervention description(s): During 3-days subjects will consume a diet with high content of fermentable residues
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: Intestinal gas production; Intestinal microbiota