title: Mesalazine (5-aminosalicylic acid) alters faecal bacterial profiles, but not mucosal proteolytic activity in diarrhoea-predominant irritable bowel syndrome.
abstract: BACKGROUND
  Imbalances in gut luminal bacteria may contribute to the pathogenesis of irritable bowel syndrome (IBS).
  
  
  OBJECTIVE
  To explore select bacteriological and anti-inflammatory effects of mesalazine (mesalamine; 5-aminosalicylic acid or 5ASA) and their relation to potential therapeutic effects in IBS.
  
  
  METHODS
  Prospective pilot study of 12 women with diarrhoea-predominant IBS. Patients received oral mesalazine (1.5 g b.d.) for 4 weeks followed by a 4-week washout phase. Molecular profiling of stool bacterial communities and IBS symptoms were assessed before, during and after mesalazine treatment. Colonic mucosal biopsies were assessed for proteolytic activity. Qualitative and quantitative effects of mesalazine on stool microbiota, mucosal proteolytic activity and IBS symptoms were assessed.
  
  
  RESULTS
  Faecal bacteria decreased by 46% on mesalazine treatment (P = 0.014), but returned to baseline during washout. Firmicutes and Bacteroidetes represented 95% of identified phylotypes, with a trend towards an increase in the proportion of Firmicutes at week 4 in symptomatic responders [median (IQR) 14% (49) increase] compared with nonresponders [median 5% (11) decrease, P = 0.088]. Rectosigmoid mucosal proteolytic activity did not change between baseline and treatment [median 23.2 (17.9) vs. 19.5 (46.7) mU activity/mg tissue, P = 0.433]. Eight of 12 (67%) patients responded favourably to mesalazine based on a global relief questionnaire, with significant decreases in days with discomfort and increases in bowel movement satisfaction.
  
  
  CONCLUSIONS
  Mesalazine treatment is associated with a decrease in faecal bacteria abundance and rebalancing of the major constituents of the microbiota. Further study of the bacteriological and anti-inflammatory properties of mesalazine in IBS is warranted.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Calgary, Calgary, AB, Canada. candrews@ucalgary.ca
authors.forename: C N
authors.initials: CN
authors.lastname: Andrews
authors.forename: T A
authors.initials: TA
authors.lastname: Griffiths
authors.forename: J
authors.initials: J
authors.lastname: Kaufman
authors.forename: N
authors.initials: N
authors.lastname: Vergnolle
authors.forename: M G
authors.initials: MG
authors.lastname: Surette
authors.forename: K P
authors.initials: KP
authors.lastname: Rioux
mesh_terms: D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001419:Bacteria / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000032:analysis; D003967:Diarrhea / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D005243:Feces / Q000382:microbiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology; D019804:Mesalamine / Q000627:therapeutic use*; D010447:Peptide Hydrolases / Q000378:metabolism*; D010865:Pilot Projects; D011446:Prospective Studies
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004269:DNA, Bacterial; D019804:Mesalamine; D010447:Peptide Hydrolases