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Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease
  1. Jane L Benjamin1,
  2. Charlotte R H Hedin1,
  3. Andreas Koutsoumpas1,
  4. Siew C Ng2,3,
  5. Neil E McCarthy4,
  6. Ailsa L Hart2,
  7. Michael A Kamm2,5,
  8. Jeremy D Sanderson1,
  9. Stella C Knight2,
  10. Alastair Forbes6,
  11. Andrew J Stagg4,
  12. Kevin Whelan1,
  13. James O Lindsay4,7
  1. 1Nutritional Sciences Division, King's College London, London, UK
  2. 2Antigen Presenting Research Group, Imperial College, London, UK
  3. 3Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong
  4. 4Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  5. 5Departments of Medicine and Gastroenterology, St Vincent's Hospital, University of Melbourne, Melbourne, Australia
  6. 6Centre for Gastroenterology and Nutrition, University College, London, UK
  7. 7Digestive Diseases Clinical Academic Unit, Barts and the London NHS Trust, London, UK
  1. Correspondence to Dr James Lindsay, Digestive Diseases Clinical Academic Unit, Barts and the London School of Medicine, The Royal London Hospital, London E1 1BB, UK; james.lindsay{at}bartsandthelondon.nhs.uk

Abstract

Introduction The commensal intestinal microbiota drive the inflammation associated with Crohn's disease. However, bacteria such as bifidobacteria and Faecalibacterium prausnitzii appear to be immunoregulatory. In healthy subjects the intestinal microbiota are influenced by prebiotic carbohydrates such as fructo-oligosaccharides (FOS). Preliminary data suggest that FOS increase faecal bifidobacteria, induce immunoregulatory dendritic cell (DC) responses and reduce disease activity in patients with Crohn's disease.

Aims and methods To assess the impact of FOS in patients with active Crohn's disease using an adequately powered randomised double-blind placebo-controlled trial with predefined clinical, microbiological and immunological end points. Patients with active Crohn's disease were randomised to 15 g/day FOS or non-prebiotic placebo for 4 weeks. The primary end point was clinical response at week 4 (fall in Crohn's Disease Activity Index of ≥70 points) in the intention-to-treat (ITT) population.

Results 103 patients were randomised to receive FOS (n=54) or placebo (n=49). More patients receiving FOS (14 (26%) vs 4 (8%); p=0.018) withdrew before the 4-week end point. There was no significant difference in the number of patients achieving a clinical response between the FOS and placebo groups in the ITT analysis (12 (22%) vs 19 (39%), p=0.067). Patients receiving FOS had reduced proportions of interleukin (IL)-6-positive lamina propria DC and increased DC staining of IL-10 (p<0.05) but no change in IL-12p40 production. There were no significant differences in the faecal concentration of bifidobacteria and F prausnitzii between the groups at baseline or after the 4-week intervention.

Conclusion An adequately powered placebo-controlled trial of FOS showed no clinical benefit in patients with active Crohn's disease, despite impacting on DC function. ISRCTN50422530.

  • Fructo-oligosaccharide
  • oligofructose
  • inulin
  • prebiotic
  • Crohn's disease
  • clinical trials
  • molecular immunology

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Footnotes

  • See Commentary, p 882

  • For further details of protocol see http://www.controlled-trials.com/ISRCTN50422530.

  • Linked articles 234369.

  • Funding This work was supported by a research grant from the Broad Medical Research Program, Los Angeles, California, USA. Sachets of fructo-oligosaccharides and placebo were provided by Beneo-Orafti, Belgium.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the National Research Ethics Service (South East Research Ethics Committee).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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