The two main phenotypes of inflammatory bowel disease (IBD)--Crohn's disease (CD) and ulcerative colitis (UC)--are chronic intestinal inflammatory disorders with a complex genetic background. Using a three-stage design, we performed a functional candidate-gene analysis of innate immune pathway in IBD. In phase I, we typed 354 SNPs from 85 innate immunity genes in 520 Dutch IBD patients (284 CD, 236 UC) and 808 controls. In phase II, ten autosomal SNPs showing association at p < 0.006 in phase I were replicated in a second cohort of 545 IBD patients (326 CD, 219 UC) and 360 controls. In phase III, four SNPs with p < 0.01 in the combined phase I and phase II analysis were genotyped in an additional 786 IBD samples (452 CD, 334 UC) and 768 independent controls. Joint analysis of 1851 IBD patients (1062 CD, 789 UC) and 1936 controls demonstrated strong association to the IL18RAP rs917997 SNP for both CD and UC (p(IBD) 1.9 x 10(-8); OR 1.35). Association in CD is independently supported by the Crohn's disease dataset of the Wellcome Trust Case Control Consortium (imputed SNP rs917997, p = 9.19 x 10(-4)). In addition, an association of the CARD9 rs10870077 SNP to CD and UC was observed (p(IBD) = 3.25 x 10(-5); OR 1.21). Both genes are located in extended haplotype blocks on 2q11-2q12 and 9q34.3, respectively. Our results indicate two IBD loci and further support the importance of the innate immune system in the predisposition to both CD and UC.

High detection rates of the causes of OGIB are feasible with VCE and DBE. Although the detection rate of VCE was superior, our results indicate that the procedures are complementary; an initial diagnostic imaging employing VCE might be followed by therapeutic and interventional DBE.

The composition of the gut microbiota is associated with various disease states, most notably inflammatory bowel disease, obesity and malnutrition. This underlines that analysis of intestinal microbiota is potentially an interesting target for clinical diagnostics. Currently, the most commonly used sample types are feces and mucosal biopsy specimens. Because sampling method, storage and processing of samples impact microbiota analysis, each sample type has its own limitations. An ideal sample type for use in routine diagnostics should be easy to obtain in a standardized fashion without perturbation of the microbiota. Rectal swabs may satisfy these criteria, but little is known about microbiota analysis on these sample types. In this study we investigated the characteristics and applicability of rectal swabs for gut microbiota profiling in a clinical routine setting in patients presenting with various gastro-intestinal disorders. We found that rectal swabs appeared to be a convenient means of sampling the human gut microbiota. Swabs can be performed on demand, whenever a patient presents; swab-derived microbiota profiles are reproducible, whether they are gathered at home by patients or by medical professionals in an outpatient setting and may be ideally suited for clinical diagnostics and large-scale studies.

In the course and prognosis of colorectal cancer (CRC), early detection and treatment are essential factors. Fecal immunochemical tests (FITs) are currently the most commonly used non-invasive screening tests for CRC and premalignant (advanced) adenomas, however, with restricted sensitivity. We hypothesized that fecal volatile organic compounds (VOCs) may serve as a diagnostic biomarker of CRC and adenomas. In this proof of concept study, we aimed to assess disease-specific VOC smellprints in fecal gas to distinguish patients with CRC and advanced adenomas from healthy controls. Fecal samples of patients who were scheduled to undergo an elective colonoscopy were collected. An electronic nose (Cyranose 320V R ) was used to measure VOC patterns in fecal gas from patients with histopathologically proven CRC, with advanced adenomas and from controls (no abnormalities seen at colonoscopy). Receiver operator characteristic curves and corresponding sensitivity and specificity for detection of CRC and advanced adenomas were calculated. A total of 157 stool samples (40 patients with CRC, 60 patients with advanced adenomas, and 57 healthy controls) were analyzed by electronic nose. Fecal VOC profiles of patients with CRC differed significantly from controls (area under curve 6 95%CI, p-value, sensitivity, specificity; 0.92 6 0.03, <0.001, 85%, 87%). Also VOC profiles of patients with advanced adenomas could be discriminated from controls (0.79 6 0.04, <0.001, 62%, 86%). The results of this proof of concept study suggest that fecal gas analysis by an electronic nose seems to hold promise as a novel screening tool for the (early) detection of advanced neoplasia and CRC.Colorectal cancer (CRC) is one of the predominant cancers, contributing to a high burden of morbidity and mortality in the United States of America and Europe. 1,2 Early detection and treatment are critical factors in the course and prognosis of CRC, and screening programs have proven to be an important means to reduce both mortality and secondary economic burden. [3][4][5] Colonoscopy is considered the gold standard for CRC and advanced adenoma screening. Fecal immunochemical tests (FIT) are currently the most commonly used non-invasive fecal screening tests. However, sensitivity of FIT for CRC is between 66-88% 6-10 depending on the cut-off values used, whereas sensitivity for advanced adenomas is disturbingly low (27-41%). 6,8,11,12 As CRC prevention programs should primarily focus on early detection of premalignant advanced adenomas, the search for novel, more accurate non-invasive screening methods remains warranted.Analysis of volatile organic compounds (VOCs) in exhaled breath has been reported as a potential non-invasive diagnostic biomarker test for lung cancer, breast cancer, malignant melanomas and CRC. [13][14][15] VOCs are gaseous carbon-based chemicals resulting from biochemical processes in the body, which are discharged by exhaled air, sweat, urine and feces. 16 VOCs in fecal gases are mainly produced by the intestinal microbiota in the colon...