P860 Combination of prebiotic FOS and adalimumab for prevention of dysbiosis in active Crohn’s disease: A pilot study

Abstract

Background: Gut microbiota in Crohn's disease (CD) patients is deficient in commensal bacteria of the phylum Firmicutes, particularly the species Faecalibacterium prausnitzii. F. prausnitzii has anti-inflammatory properties and in patients with ileal CD, defective mucosal colonisation by F. prausnitzii increases the risk of postoperative recurrence. Some authors have proposed that F. prausnitzii depletion (i.e. abundance below 109 copies per g/faeces) could be a diagnostic marker of CD. F. prausnitzii counts in faecal samples increase significantly after daily FOS intake in healthy volunteers. Experimental studies suggest anti-TNF failure depends on dysbiosis. The aim of this study was to evaluate the effect of combining FOS and adalimumab on dysbiosis in faecal samples from Crohn's disease patients. Method(s): CD patients who required treatment with an anti-TNF agent by standard clinical practice and who chose adalimumab, were proposed to participate in the study to receive co-treatment with FOS. All patients received FOS (Actilight Beghin Meiji, Paris, France) 6 g p.o. once daily, starting two weeks before Adalimumab and in combination for the next 12 weeks. Adalimumab was administered according to standard schedule. Total bacteria, F. prausnitzii, and Bifidobacteria counts were assessed by qPCR in fecal samples at time points-2, 0, 2, 6 and 14 weeks. Crohn's disease activity index (CDAI), CRP and fecal calprotectin were assessed at each time-point. Result(s): Thirty-four patients were included, median age of 41 years, 68% female and 18% current smokers. Fifty-three percent had disease located in terminal ileum, 59% a non-stricturing, non-penetrating behaviour, 29% perianal disease and 18% had extraintestinal manifestations. At baseline, 24 patients had F. prausnitzii levels below 109 CFU/g (median 1.76 x 107). Lower F. prausnitzii levels were associated with stricturing disease and a previous intestinal resection (p < 0.05). FOS did not significantly increase F. prausnitzii levels, but it had an effect on Bifidobacteria counts (median baseline 4.78 x 107 vs. Week 6 1.54 x 109, p < 0.01). Adalimumab treatment significantly lowered CDAI scores (median delta 23) and calprotectin levels (median delta 99) regardless of F. prausnitzii levels at baseline. Two patients with previous depletion of F. prausnitzii restored levels to above 109 CFU/g, both achieving disease remission at the end of the study. Conclusion(s): Adalimumab improved clinical scores and inflammatory markers. Combination with FOS did not increase F. prausnitzii levels but Bifidobacteria were significantly incremented. Most patients presented abnormally low F. prausnitzii levels at baseline. Depletion of F. prausnitzii was related to a past severe disease course, but it did not affect response to Adalimumab. Restoring F. prausnitzii to normal levels was linked to good clinical outcome.