Randomised, double-blind, placebo-controlled trial of fructo-oligosaccharides in active Crohn's disease.
BACKGROUND
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Nutritional Sciences Division, King's College London, London, UK.
Jane L
JL
Benjamin
Charlotte R H
CR
Hedin
Andreas
A
Koutsoumpas
Siew C
SC
Ng
Neil E
NE
McCarthy
Ailsa L
AL
Hart
Michael A
MA
Kamm
Jeremy D
JD
Sanderson
Stella C
SC
Knight
Alastair
A
Forbes
Andrew J
AJ
Stagg
Kevin
K
Whelan
James O
JO
Lindsay
D000328:Adult; D001644:Bifidobacterium / Q000302:isolation & purification; D003424:Crohn Disease / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D003713:Dendritic Cells / Q000276:immunology; D004311:Double-Blind Method; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009844:Oligosaccharides / Q000009:adverse effects / Q000627:therapeutic use*; D056692:Prebiotics / Q000009:adverse effects; D012007:Rectum / Q000276:immunology; D016896:Treatment Outcome
D009844:Oligosaccharides; D056692:Prebiotics; C116580:fructooligosaccharide