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Gut 2005;54:242-249
© 2005 by BMJ Publishing Group Ltd & British Society of Gastroenterology


INFLAMMATORY BOWEL DISEASE

Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlled pilot trial

E Furrie1, S Macfarlane1, A Kennedy1, J H Cummings2, S V Walsh3, D A O’Neil4, G T Macfarlane1

1 MRC Microbiology and Gut Biology Group, University of Dundee, Ninewells Hospital Medical School, Dundee, UK
2 Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital Medical School, Dundee, UK
3 Department of Pathology, Ninewells Hospital and Medical School, Dundee, UK
4 Immunology Unit, Rowett Research Institute, Aberdeen, UK

Correspondence to:
Correspondence to:
Dr E Furrie
Microbiology and Gut Biology Group, University of Dundee, Ninewells Hospital Medical School, Dundee DD1 9SY, UK; e.furrie{at}dundee.ac.uk

Background and aims: Ulcerative colitis (UC) is an acute and chronic inflammatory disease of the large bowel with unknown aetiology. The immune response against normal commensal microorganisms is believed to drive inflammatory processes associated with UC. Therefore, modulation of bacterial communities on the gut mucosa, through the use of probiotics and prebiotics, may be used to modify the disease state.

Methods: A synbiotic was developed for use in UC patients combining a probiotic, Bifidobacterium longum, isolated from healthy rectal epithelium, and a prebiotic (Synergy 1), a preferential inulin-oligofructose growth substrate for the probiotic strain. Treatment was employed in a double blinded randomised controlled trial using 18 patients with active UC for a period of one month. Clinical status was scored and rectal biopsies were collected before and after treatment, and transcription levels of epithelium related immune markers were measured.

Results: Sigmoidoscopy scores (scale 0–6) were reduced in the test group (start 4.5 (1.4), end 3.1 (2.5)) compared with placebo (start 2.6 (2.1), end 3.2 (2.2)) (p = 0.06). mRNA levels for human beta defensins 2, 3, and 4, which are strongly upregulated in active UC, were significantly reduced in the test group after treatment (p = 0.016, 0.038, and 0.008, respectively). Tumour necrosis factor {alpha} and interleukin 1{alpha}, which are inflammatory cytokines that drive inflammation and induce defensin expression, were also significantly reduced after treatment (p = 0.018 and 0.023, respectively). Biopsies in the test group had reduced inflammation and regeneration of epithelial tissue.

Conclusions: Short term synbiotic treatment of active UC resulted in improvement of the full clinical appearance of chronic inflammation in patients receiving this therapy.


Abbreviations: BHI, bowel habit index; CAI, clinical activity index; CRP, C reactive protein; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HS, histology score; hBD, human beta defensin; IBD, inflammatory bowel disease; IL-1{alpha}, interleukin 1{alpha}; IL-10, interleukin 10; PCR, polymerase chain reaction; SS, sigmoidoscopy score; TNF-{alpha}, tumour necrosis factor {alpha}; UC, ulcerative colitis; WC, Wilkins-Chalgren

Keywords: synbiotic therapy; Bifidobacterium longum; synergy I; ulcerative colitis; human beta defensins; mucosal immunology




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