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We evaluated a novel 'protected' biopsy method to reliably ascertain the spatial distribution of the mucosa-adherent colonic microbiota. Apart from minor differences at genus level, overall similarities along the colon were high between the various areas, irrespective of protected or unprotected sampling.

Background & Aims Several case series have reported the effects of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). We assessed the efficacy and safety of FMT for patients with UC in a double-blind randomized trial. Methods Patients with mild to moderately active UC (n = 50) were assigned to groups that underwent FMT with feces from healthy donors or were given autologous fecal microbiota (control); each transplant was administered via nasoduodenal tube at the start of the study and 3 weeks later. The study was performed at the Academic Medical Center in Amsterdam from June 2011 through May 2014. The composite primary end point was clinical remission (simple clinical colitis activity index scores ≤2) combined with ≥1-point decrease in the Mayo endoscopic score at week 12. Secondary end points were safety and microbiota composition by phylogenetic microarray in fecal samples. Results Thirty-seven patients completed the primary end point assessment. In the intention-to-treat analysis, 7 of 23 patients who received fecal transplants from healthy donors (30.4%) and 5 of 25 controls (20.0%) achieved the primary end point ( P = .51). In the per-protocol analysis, 7 of 17 patients who received fecal transplants from healthy donors (41.2%) and 5 of 20 controls (25.0%) achieved the primary end point ( P = .29). Serious adverse events occurred in 4 patients (2 in the FMT group), but these were not considered to be related to the FMT. At 12 weeks, the microbiota of responders in the FMT group was similar to that of their healthy donors; remission was associated with proportions of Clostridium clusters IV and XIVa. Conclusions In this phase 2 trial, there was no statistically significant difference in clinical and endoscopic remission between patients with UC who received fecal transplants from healthy donors and those who received their own fecal microbiota, which may be due to limited numbers. However, the microbiota of responders had distinct features from that of nonresponders, warranting further study. ClinicalTrials.gov Number: NCT01650038.

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.The ISME Journal advance online publication, 11 April 2017; doi:10.1038/ismej.2017.44.

Reported epidemiology and phenotype distributions vary widely and disease burden of inflammatory bowel disease (IBD) is poorly described. Our aim was to establish these features in a population-based cohort covering 319 976 inhabitants. Furthermore, differences between tertiary referral and peripheral hospital patients were quantified. IBD patients in the adherence area of three peripheral hospitals (2004-2012) were included. Medical and surgical treatment data were obtained. Quality of life and disease activity were evaluated. An outpatient cohort from a tertiary referral centre was accrued. A total of 1461 patients were included: 761 (52.1%) with ulcerative colitis (UC), 579 (39.5%) with Crohn's disease (CD) and 121 (8.3%) with IBD-unspecified. Point prevalence of IBD was 432.1 per 100 000 inhabitants in 2010, which increased significantly over time, P-value of less than 0.0001. The mean annual incidence was 17.2 for UC, 10.5 for CD and 2.2 for IBD-unspecified. Tertiary referral Crohn's patients used thiopurines and biological therapy and underwent surgery significantly more often than patients in peripheral hospitals (P

Ulcerative colitis (UC) is thought to originate from a disbalance in the interplay between the gut microbiota and the innate and adaptive immune system. Apart from the bacterial microbiota, there might be other organisms, such as parasites or viruses, that could play a role in the aetiology of UC. The primary objective of this study was to compare the prevalence of Blastocystis sp. in a cohort of patients with active UC and compare that to the prevalence in healthy controls. We studied patients with active UC confirmed by endoscopy included in a randomised prospective trial on the faecal transplantation for UC. A cohort of healthy subjects who served as donors in randomised trials on faecal transplantation were controls. Healthy subjects did not have gastrointestinal symptoms and were extensively screened for infectious diseases by a screenings questionnaire, extensive serologic assessment for viruses and stool analysis. Potential parasitic infections such as Blastocystis were diagnosed with the triple faeces test (TFT). The prevalence of Blastocystis sp. were compared between groups by Chi-square testing. A total of 168 subjects were included, of whom 45 had active UC [median age 39.0 years, interquartile range (IQR) 32.5–49.0, 49 % male] and 123 were healthy subjects (median age 27 years, IQR 22.0–37.0, 54 % male). Blastocystis sp. was present in the faeces of 40/123 (32.5 %) healthy subjects and 6/45 (13.3 %) UC patients (p = 0.014). Infection with Blastocystis is significantly less frequent in UC patients as compared to healthy controls.

Background: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that is strongly associated with a particular phenotype of inflammatory bowel disease (IBD) with right-sided colonic involvement. In IBD, several studies demonstrated significant aberrancies in the intestinal microbiota in comparison with healthy controls. We aimed to explore the link between IBD and PSC by studying the intestinal mucosa-adherent microbiota in PSC and ulcerative colitis (UC) patients and noninflammatory controls. Methods: We included 12 PSC patients, 11 UC patients, and nine noninflammatory controls. The microbiota composition was determined in ileocecal biopsies from each patient by 16S rRNA-based analyses using the human intestinal tract chip. Results: Profiling of the mucosa-adherent microbiota of PSC patients, UC patients, and noninflammatory controls revealed that these groups did not cluster separately based on microbiota composition. At the genus-like level, the relative abundance of uncultured Clostridiales II was significantly lower (almost 2-fold) in PSC (0.26 ± 0.10%) compared with UC (0.41 ± 0.29%) and controls (0.49 ± 0.25%) ( p = 0.02). Diversity and richness in the microbiota composition differed across the groups and were significantly lower in PSC patients compared with noninflammatory controls ( p = 0.04 and p = 0.02, respectively). No significant differences were found in evenness. Conclusions: Reduced amounts of uncultured Clostridiales II in PSC biopsies in comparison with UC and healthy controls can be considered a signature of a compromised gut, as we have recently observed that this group of as yet uncultured Firmicutes correlates significantly with health.

Background and aims: The epidemiology of inflammatory bowel disease (IBD) is changing. In Europe, recent incidence and prevalence rates are lacking. The primary objective of this study is to update incidence and prevalence figures in a large well-phenotyped populationbased IBD cohort.Methods: All IBD patients living in the adherence area of 2 non-academic hospitals between 20042010 were identified. Patients were searched in 3 independent hospital databases case finding sources. 1378 Possible IBD cases were scrutinized, IBD diagnosis was based on established clinical, endoscopic and pathologic criteria. Location and behaviour of IBD was reported according to the Montreal classification. Results: 768 IBD patients were included. 255 (33.2%) patients were diagnosed with Crohn's disease (CD), 432 (56.3%) with ulcerative colitis (UC) and 81 (10.5%) with IBD-Unspecified (IBDU). The male-female ratio of IBD was 1:1.3 (P

AIM: To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category, on an intention-to-treat basis. RESULTS: We included 45 studies; 34 on Clostridium difficile-infection (CDI), 7 on inflammatory bowel disease, 1 on metabolic syndrome, 1 on constipation, 1 on pouchitis and 1 on irritable bowel syndrome (IBS). In CDI 90% resolution of diarrhea in 33 case series (n = 867) was reported, and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial (RCT) (n = 16). In ulcerative colitis (UC) remission rates of 0% to 68% were found (n = 106). In Crohn's disease (CD) (n = 6), no benefit was observed. In IBS, 70% improvement of symptoms was found (n = 13). 100% Reversal of symptoms was observed in constipation (n = 3). In pouchitis, none of the patients (n = 8) achieved remission. One RCT showed significant improvement of insulin sensitivity in metabolic syndrome (n = 10). Serious adverse events were rare. CONCLUSION: FMT is highly effective in CDI, and holds promise in UC. As for CD, chronic constipation, pouchitis and IBS data are too limited to draw conclusions. FMT increases insulin sensitivity in metabolic syndrome

there is current debate about a causal relation between retinoid treatment and inflammatory bowel disease (IBD). Patients have claimed that they developed acute intestinal inflammation during isotretinoin treatment or to develop inflammatory bowel disease (IBD) weeks or even years after cessation of the medication. We have previously shown that isotretinoin treatment has no adverse effects in two mouse models of inflammatory bowel disease [1]. Since the gut microbiota can metabolize retinoids, we investigated whether administration of retinoids might change the gut microbiota composition in a way that is favorable for the development of IBD. Methods: Balb/c mice were treated with isotretinoin (30mg/kg bodyweight) or vehicle orally for 2 weeks and kept for further 4 weeks to study potential direct and long-term effects. Fecal samples were collected before treatment, directly after the treatment period and four weeks later for analysis of gut microbiota composition by 16S rRNA gene sequencing on the GS-Flx 454 platform. Sequencing data were analyzed with the software QIIME to determine OTUs, calculate the relative abundance for each group and time point and to general principal coordinate analysis plots. Results: Principle coordinate analysis showed no formation of clusters neither depending on treatment nor on time point of investigation indicating no fundamental differences between the gut microbiota composition of isotretinoin or vehicle treated animals or between the different time points studied. Some differences with regard to alpha and beta diversity between the different treatment groups as well as between the different time points studied were observed and are currently under further investigation. Conclusions: Preliminary results with QIIME showed no substantial differences between isotretinoin and vehicle treated animals indicating that isotretinoin treatment had no fundamental effect on the composition of the murine gut microbiota. We are currently investigating the variations in alpha and beta diversity that were observed between groups exposed to isotretinoin and vehicle, as well as between the different time points.