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Diet plays an important role in the development and progression of inflammatory bowel disease (IBD, comprising Crohn's disease (CD) and ulcerative colitis (UC)). However, little is known about the extent to which different diets reflect inflammation in IBD beyond measures such as faecal calprotectin or C-reactive protein. In this study, we aimed to unravel associations between dietary patterns and circulating inflammatory proteins in patients with IBD. Plasma concentrations of 73 different inflammation-related proteins were measured in 454 patients with IBD by proximity extension assay (PEA) technology. Food frequency questionnaires (FFQ) were used to assess habitual diet. Principal component analysis (PCA) was performed to extract data-driven dietary patterns. To identify associations between dietary patterns and plasma proteins, we used general linear models adjusting for age, sex, BMI, plasma storage time, smoking, surgical history and medication use. Stratified analyses were performed for IBD type, disease activity and protein intake. A high-sugar diet was strongly inversely associated with fibroblast growth factor-19 (FGF-19) independent of IBD type, disease activity, surgical history and deviance from recommended protein intake (false discovery rate (FDR) < 0.05). Conversely, a Mediterranean-style pattern was associated with higher FGF-19 levels (FDR < 0.05). A pattern characterised by high alcohol and coffee intake was positively associated with CCL11 (eotaxin-1) levels and with lower levels of IL-12B (FDR < 0.05). All results were replicated in CD, whereas only the association with FGF-19 was significant in UC. Our study suggests that dietary habits influence distinct circulating inflammatory proteins implicated in IBD and supports the pro- and anti-inflammatory role of diet. Longitudinal measurements of inflammatory markers, also postprandial, are needed to further elucidate the diet-inflammation relationship.

Background Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn’s disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To aid patient stratification, polygenetic risk scores have been identified as predictors of response to anti-TNFα therapy. We aimed to replicate the association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients, to establish its clinical validity. Materials and methods Primary non-response, primary response, durable response and loss of response to anti-TNFα therapy was retrospectively assessed for each patient using stringent definitions. Genome wide genotyping was performed and previously described polygenetic risk scores for primary non-response and durable response were calculated. We compared polygenetic risk scores between patients with primary response and primary non-response, and between patients with durable response and loss of response, using separate analyses for CD and UC. Results Out of 334 patients with CD, 15 (4%) patients met criteria for primary non-response, 221 (66%) for primary response, 115 (34%) for durable response and 35 (10%) for loss of response. Out of 112 patients with UC, 12 (11%) met criteria for primary non-response, 68 (61%) for primary response, 19 (17%) for durable response and 20 (18%) for loss of response. No significant differences in polygenetic risk scores were found between primary non-responders and primary responders, and between durable responders and loss of responders. Conclusions We could not replicate the previously reported association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients with CD or UC. Currently, there is insufficient evidence to use polygenetic risk scores to predict response to anti-TNFα therapy in patients with IBD.

Background: The understanding of gender differences in inflammatory bowel disease (IBD) patients is an important step towards tailored treatment for the individual patient. The aim of this study was to compare disease phenotype, clinical manifestations, disease activity, and healthcare utilization between men and women with Crohn's disease (CD) and ulcerative colitis (UC).Methods: Two multicenter observational cohort studies with a prospective design were used to explore the differences between men and women regarding demographic and phenotypic characteristics and healthcare utilization. Detailed data on IBD-phenotype was mainly available from the Dutch IBD Biobank, while the COIN cohort provided healthcare utilization data.Results: In the Dutch IBD Biobank study, 2118 CD patients and 1269 UC patients were analyzed. Female CD patients were more often current smokers, and male UC patients were more often previous smokers. Early onset CD (Conclusions: Sex differences in patients with IBD include age of onset, disease location, and EIM prevalence. No large differences in therapeutic management of IBD were observed between men and women with IBD.

Background Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data generated from the same IBD patients. Construction and content We initiated the 1000IBD project (https://1000ibd.org) to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1215 participants have been enrolled in the project and enrolment is on-going. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing. Utility and discussion All molecular data generated within the 1000IBD project will be shared on the European Genome-Phenome Archive (https://ega-archive.org, accession no: EGAS00001002702). The first data release, detailed in this announcement and released simultaneously with this publication, will contain basic phenotypes for 1215 participants, genotypes of 314 participants and gut microbiome data from stool samples (315 participants) and biopsies (107 participants) generated by tag sequencing the 16S gene. Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models. Conclusions We report on the establishment and future development of the 1000IBD project: the first comprehensive multi-omics dataset aimed at discovering IBD biomarker profiles and treatment targets. Electronic supplementary material The online version of this article (10.1186/s12876-018-0917-5) contains supplementary material, which is available to authorized users.

ObjectivePatients with IBD display substantial heterogeneity in clinical characteristics. We hypothesise that individual differences in the complex interaction of the host genome and the gut microbiota can explain the onset and the heterogeneous presentation of IBD. Therefore, we performed a case–control analysis of the gut microbiota, the host genome and the clinical phenotypes of IBD.DesignStool samples, peripheral blood and extensive phenotype data were collected from 313 patients with IBD and 582 truly healthy controls, selected from a population cohort. The gut microbiota composition was assessed by tag-sequencing the 16S rRNA gene. All participants were genotyped. We composed genetic risk scores from 11 functional genetic variants proven to be associated with IBD in genes that are directly involved in the bacterial handling in the gut: NOD2, CARD9, ATG16L1, IRGM and FUT2.ResultsStrikingly, we observed significant alterations of the gut microbiota of healthy individuals with a high genetic risk for IBD: the IBD genetic risk score was significantly associated with a decrease in the genus Roseburia in healthy controls (false discovery rate 0.017). Moreover, disease location was a major determinant of the gut microbiota: the gut microbiota of patients with colonic Crohn's disease (CD) is different from that of patients with ileal CD, with a decrease in alpha diversity associated to ileal disease (p=3.28×10−13).ConclusionsWe show for the first time that genetic risk variants associated with IBD influence the gut microbiota in healthy individuals. Roseburia spp are acetate-to-butyrate converters, and a decrease has already been observed in patients with IBD.