P708 What causes recurrence of Crohn's Disease after intestinal resection? A prospective evaluation of microbiota, smoking and anti-TNF therapy. Results from the POCER study
E. Wright*1, M. Kamm1, 2, J. Wagner3, S.M. Teo4, P. De Cruz1, A. Hamilton1, K. Ritchie1, M. Inouye4, C. Kirkwood3
1St Vincent's Hospital & University of Melbourne, Gastroenterology, Melbourne, Australia, 2Imperial College London, Medicine, London, United Kingdom, 3Murdoch Children's Research Institute, Enteric Virus Group, Melbourne, Australia, 4The University of Melbourne, Pathology, Melbourne, Australia
The intestinal microbiota is the antigenic drive in Crohn's. It is also likely to be responsible for disease recurrence after intestinal resection. We aimed to identify microbiota predictive of, or associated with, disease recurrence, remission, smoking and adalimumab therapy.
141 mucosal samples from 34 Crohn's disease patients were obtained at surgical resection (baseline) and from the ileum and anastomosis at colonoscopy 6 and/or 18 months post-operatively. 28 control samples were obtained; 12 colonic samples from healthy patients with a normal colon (healthy controls) and 16 ileal and anastomosis samples from 8 patients who had previously undergone right hemicolectomy for colon cancer (surgical controls). Endoscopic recurrence in Crohn's patients was assessed using the Rutgeerts score. Mucosal 16s ribosomal profiling was performed using the MiSeq Illumina platform.
Crohn's disease was associated with reduced bacterial diversity when compared to healthy controls but not surgical controls (Shannon Diversity Index; t-test: p=0.012 and p=0.552 respectively). Bacterial composition (beta diversity) differed significantly between Crohn's disease and both healthy (p=0.024) and surgical (p=0.038) controls, and changed within Crohn's patients over time, but did not differ significantly between those with and without endoscopic recurrence. However significant taxonomic differences between recurrence and remission included increased Proteus (p=0.019) and decreased genera from the Firmicutes phylum including Faecalibacterium (p=0.004). No significant differences were observed in alpha or beta diversity between smokers vs. non-smokers and between adalimumab treatment vs. no adalimumab treatment. Smoking was associated with significantly elevated levels of Proteus (p=0.013) and lower levels of Phascolarctobacterium (p=0.028) and Faecalibacterium (p=0.029). Low abundance of Faecalibacterium and smoking were both independently associated with recurrence (OR 5.5 (CI 1.8-17) p=0.002 and OR 3.3 (CI 1-11) p=0.049) respectively.
Crohn's disease is associated with a microbial signature distinct from health. Surgical resection alone may be responsible for some, but not all, of the taxonomic differences observed in patients following intestinal resection in Crohn's disease. Microbial factors, such as the presence of Faecalibacterium, and smoking may influence post-operative Crohn's disease recurrence through independent mechanisms. The mechanism by which anti-TNF therapy prevents recurrence post-operatively does not appear to have a microbial basis.