No abstract

Faecal microbiota transplantation (FMT) may contribute towards disease remission in ulcerative colitis (UC), but it is unknown which factors determine long-term effect of treatment. Here, we aimed to identify bacterial signatures associated with sustained remission. To this end, samples from healthy donors and UC patients-grouped into responders and non-responders at a primary end point (week 12) and further stratified by sustained clinical remission and relapse assessed at ⩾1-year follow-up were analysed, comparing the efficacy of FMT from either a healthy donor or autologous faeces. Microbiota composition was determined with a 16S rRNA gene-based phylogenetic microarray on faecal and mucosal samples, and functional profiles were predicted using PICRUSt with quantitative PCR verification of the butyrate production capacity; short-chain fatty acids were measured in faecal samples. At baseline, UC patients showed reduced amounts of bacterial groups from the Clostridium cluster XIVa, and significantly higher levels of Bacteroidetes as compared with donors. These differences were reduced after FMT mostly in responders. Sustained remission was associated with known butyrate producers and overall increased butyrate production capacity, while relapse was associated with Proteobacteria and Bacteroidetes. Ruminococcus gnavus was found at high levels in donors of failed FMT. A microbial ecosystem rich in Bacteroidetes and Proteobacteria and low in Clostridium clusters IV and XIVa observed in UC patients after FMT was predictive of poor sustained response, unless modified with a donor microbiota rich in specific members from the Clostridium clusters IV and XIVa. Additionally, sustained response was associated with restoration of the butyrate production capacity.

between subjects with UC (n=41), CD (n=32) and their healthy twin at time of symptom onset. Medication and Stress: On review of all IBD sufferers, 7.1% (8/112) and 13.4% (15/112) used NSAIDS and antibiotics within 3 months preceding onset. 48.2% (54/112) reported significant stress within the year before diagnosis. Time of onset in concordant pairs: The mean lag between diagnosis of concordant pairs was 7 years 5 months. Conclusions: Concordance of twin pairs with CD is in keeping with the literature. UC concordance is greater than previously quoted. However DZ and MZ concordance of UC twins is similar inferring low heritability. DZ UC pair concordance is 4 fold expected non twin sibling concordance [2], suggesting early environment to be important. This study supports an associaton between diet, stress and gastrointestinal infection with IBD onset. The lack of associatoin with smoking at incidence may reflect sample size. References:[1] Brant S, (2012) Background: An aberrant microbiota has been implicated in the pathophysiology of ulcerative colitis (UC) and several case series reported favorable effects of faecal microbiota transplantation (FMT). We aimed to assess the efficacy FMT in active UC patients in a randomized parallel group study. Methods: Patients with mild-moderate UC (Simple Clinical Colitis Activity Index [SCCAI] score of 4-11 and a Mayo endoscopic score of at least 1) were randomly assigned (1:1) to FMT derived from faeces from a healthy donor: FMT-D or their own faeces used as a placebo: FMT-P. FMT was administered via a naso-duodenal tube at week 0 and 3. Patients, physicians and endoscopists were blinded, with exception of the nurse who performed randomisation and prepared the faeces filtered with normal saline. The composite primary endpoint was clinical remission (SCCAI score 2 or lower) and endoscopic response (at least 1 point decrement on the Mayo endoscopic score) at week 12. Main secondary endpoints were microbiota composition in faecal samples and safety. Results: Of 50 patients who were screened, 48 were randomised (23 to FMT-D and 25 to FMT-P. In the ITT analysis, seven out of 23 patients (30.4%) in the donor arm versus five out of 25 patients in the placebo