The purpose of the trial is to define the clinical benefit and possible mediators of the benefit of mesalazine in Irritable Bowel Syndrome (IBS) with diarrhoea.

The investigators will therefore evaluate symptoms (primarily bowel frequency) and markers reflecting mast cell activation and small bowel tone.

Inclusion Criteria:

1. Male or Female patients aged 18-75 years old able to give informed consent.

2. Patients should all have had a colonoscopy or a sigmoidoscopy within the last 12 months to exclude microscopic colitis. (If not, but they have had a negative colonoscopy within 5 years and symptoms are unchanged, then a sigmoidoscopy and mucosal biopsy of the left colon would be sufficient to exclude microscopic colitis).

3. IBS-D Patients meeting Rome III criteria prior to screening phase.

4. Patients with ≥ 25% soft (score > 4) and < 25% hard (score 1 or 2) stools during the screening phase, as scored by the daily symptom and stool diary*.

5. Patients with a stool frequency of 3 or more per day for 2 or more days per week during the screening phase*.

6. Satisfactory completion of the daily stool and symptom diary during the screening phase at the discretion of the investigator.

7. Women of child bearing potential willing or able to use at least one highly effective contraceptive method throughout the study. In the context of this study, an effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as: implants, injectables, combined oral contraceptives, sexual abstinence or vasectomised partner.

   • If inclusion criterion 4 and/or 5 is/are not met but the results are considered atypical (as observed from medical history and patient recall) then the patient can be re-screen on 1 occasion only.

Exclusion Criteria:

1. Women who are pregnant or breast feeding

2. Prior abdominal surgery which may cause bowel symptoms similar to IBS (note appendectomy and cholecystectomy will not be an exclusion)

3. Patients unable to stop anti-muscarinics, anti-spasmodics, high dose tricyclic antidepressants (i.e. above 50 mg/day), opiates/anti-diarrhoeal drugs*, NSAIDs (occasional over the counter use and topical formulations are allowed), long-term antibiotics, other anti-inflammatory drugs or 5-ASA containing drugs.

4. Patients on selective serotonin re-uptake inhibitors and low dose tricyclic antidepressants (i.e. up to 50 mg/day) for at least 3 months previous unwilling to remain on a stable dose for the duration of the trial.

5. Patients with other gastro-intestinal diseases including colitis and Crohn's disease.

6. Patients with the following conditions: Renal impairment, severe hepatic impairment or salicylate hypersensitivity.

7. Patients currently participating in another trial or have been in a trial within the previous 3 months

8. Patients who in the opinion of the investigator are considered unsuitable due to inability to comply with instructions

9. Patients with serious concomitant diseases e.g. cardiovascular, respiratory, neurological etc.

   • Loperamide is allowed as rescue medication through-out the trial, however if > 2 doses / week are taken during the screening phase then they are not eligible, though they can be re-screened on 1 occasion only.