title: Identification of an Intestinal Microbiota Signature Associated With Severity of Irritable Bowel Syndrome.
abstract: We have limited knowledge about the association between the composition of the intestinal microbiota and clinical features of irritable bowel syndrome (IBS). We collected information on the fecal and mucosa-associated microbiota of patients with IBS and evaluated whether these were associated with symptoms.
  
  
  
  We collected fecal and mucosal samples from adult patients who met the Rome III criteria for IBS at a secondary/tertiary care outpatient clinics in Sweden, as well as from healthy subjects. The exploratory set comprised 149 subjects (110 with IBS and 39 healthy subjects); 232 fecal samples and 59 mucosal biopsy samples were collected and analyzed by 16S ribosomal RNA targeted pyrosequencing. The validation set comprised 46 subjects (29 with IBS and 17 healthy subjects); 46 fecal samples, but no mucosal samples, were collected and analyzed. For each subject, we measured exhaled H2and CH4, oro-anal transit time, and the severity of psychological and gastrointestinal symptoms. Fecal methanogens were measured by quantitative polymerase chain reaction. Numerical ecology analyses and a machine learning procedure were used to analyze the data.
  
  
  
  Fecal microbiota showed covariation with mucosal adherent microbiota. By using classic approaches, we found no differences in fecal microbiota abundance or composition between patients with IBS vs healthy patients. A machine learning procedure, a computational statistical technique, allowed us to reduce the 16S ribosomal RNA data complexity into a microbial signature for severe IBS, consisting of 90 bacterial operational taxonomic units. We confirmed the robustness of the intestinal microbial signature for severe IBS in the validation set. The signature was able to discriminate between patients with severe symptoms, patients with mild/moderate symptoms, and healthy subjects. By using this intestinal microbiota signature, we found IBS symptom severity to be associated negatively with microbial richness, exhaled CH4, presence of methanogens, and enterotypes enriched with Clostridiales or Prevotella species. This microbiota signature could not be explained by differences in diet or use of medications.
  
  
  
  In analyzing fecal and mucosal microbiota from patients with IBS and healthy individuals, we identified an intestinal microbiota profile that is associated with the severity of IBS symptoms.
  
  
  
  NCT01252550.
authors.affiliation: Danone Nutricia Research, Palaiseau, France; French National Institute for Agricultural Research (INRA) MetaGenoPolis, Jouy en Josas, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Tap
authors.affiliation: Danone Nutricia Research, Palaiseau, France. Electronic address: muriel.derrien@danone.com.
authors.forename: Muriel
authors.initials: M
authors.lastname: Derrien
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Centre for Person-Centered Care, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Törnblom
authors.affiliation: Danone Nutricia Research, Palaiseau, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Brazeilles
authors.affiliation: Danone Nutricia Research, Palaiseau, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cools-Portier
authors.affiliation: French National Institute for Agricultural Research (INRA) MetaGenoPolis, Jouy en Josas, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Doré
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Stine
authors.initials: S
authors.lastname: Störsrud
authors.affiliation: Danone Nutricia Research, Palaiseau, France.
authors.forename: Boris
authors.initials: B
authors.lastname: Le Nevé
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Microbiology and Immunology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; School of Health and Education, University of Skövde, Skövde, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Öhman
authors.affiliation: Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Centre for Person-Centered Care, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Center for Functional GI and Motility Disorders, University of North Carolina, Chapel Hill, North Carolina. Electronic address: magnus.simren@medicine.gu.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Simrén
mesh_terms: D000328:Adult; D001439:Bacteroides / Q000302:isolation & purification; D001944:Breath Tests; D016022:Case-Control Studies; D000068016:Eubacteriales / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000032:analysis*; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D005772:Gastrointestinal Transit; D006801:Humans; D006859:Hydrogen / Q000032:analysis; D007413:Intestinal Mucosa / Q000382:microbiology*; D043183:Irritable Bowel Syndrome / Q000382:microbiology* / Q000503:physiopathology; D000069550:Machine Learning; D008297:Male; D008697:Methane / Q000032:analysis; D017012:Methanobacteriales / Q000302:isolation & purification; D064307:Microbiota; D018720:Prevotella / Q000302:isolation & purification; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000032:analysis*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D004269:DNA, Bacterial; D012336:RNA, Ribosomal, 16S; D006859:Hydrogen; D008697:Methane
keywords: Bacteria; Functional Bowel Disorder; Microbiome