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Publikacije (112)

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T. D. De Munck, Pauline Verhaegh, C. Spooren, Z. Mujagic, Tobias Wienhold, D. Jonkers, A. Masclee, G. Koek et al.

Robert van Vorstenbosch, Hao Cheng, D. Jonkers, J. Penders, Erik Schoon, A. Masclee, F. J. Schooten, A. Smolinska et al.

Colorectal cancer (CRC) has been associated with changes in volatile metabolic profiles in several human biological matrices. This enables its non-invasive detection, but the origin of these volatile organic compounds (VOCs) and their relation to the gut microbiome are not yet fully understood. This systematic review provides an overview of the current understanding of this topic. A systematic search using PubMed, Embase, Medline, Cochrane Library, and the Web of Science according to PRISMA guidelines resulted in seventy-one included studies. In addition, a systematic search was conducted that identified five systematic reviews from which CRC-associated gut microbiota data were extracted. The included studies analyzed VOCs in feces, urine, breath, blood, tissue, and saliva. Eight studies performed microbiota analysis in addition to VOC analysis. The most frequently reported dysregulations over all matrices included short-chain fatty acids, amino acids, proteolytic fermentation products, and products related to the tricarboxylic acid cycle and Warburg metabolism. Many of these dysregulations could be related to the shifts in CRC-associated microbiota, and thus the gut microbiota presumably contributes to the metabolic fingerprint of VOC in CRC. Future research involving VOCs analysis should include simultaneous gut microbiota analysis.

Marlijne C G de Graaf, J. Scheijen, C. Spooren, Z. Mujagic, M. Pierik, E. Feskens, D. Keszthelyi, C. Schalkwijk et al.

A Western diet comprises high levels of dicarbonyls and advanced glycation endproducts (AGEs), which may contribute to flares and symptoms in inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). We therefore investigated the intake of dietary dicarbonyls and AGEs in IBD and IBS patients as part of the habitual diet, and their association with intestinal inflammation. Food frequency questionnaires from 238 IBD, 261 IBS as well as 195 healthy control (HC) subjects were used to calculate the intake of dicarbonyls methylglyoxal, glyoxal, and 3-deoxyglucosone, and of the AGEs Nε-(carboxymethyl)lysine, Nε-(1-carboxyethyl)lysine and methylglyoxal-derived hydroimidazolone-1. Intestinal inflammation was assessed using faecal calprotectin. The absolute dietary intake of all dicarbonyls and AGEs was higher in IBD and HC as compared to IBS (all p < 0.05). However, after energy-adjustment, only glyoxal was lower in IBD versus IBS and HC (p < 0.05). Faecal calprotectin was not significantly associated with dietary dicarbonyls and AGEs in either of the subgroups. The absolute intake of methylglyoxal was significantly higher in patients with low (<15 μg/g) compared to moderate calprotectin levels (15–<50 μg/g, p = 0.031). The concentrations of dietary dicarbonyls and AGEs generally present in the diet of Dutch patients with IBD or IBS are not associated with intestinal inflammation, although potential harmful effects might be counteracted by anti-inflammatory components in the food matrix.

I. Han-Geurts, Z. Mujagic, M. Blanker

Anal complaints are common, often disabling and may have a big impact on quality of life. Treatment is aimed at improving underlying conditions and starts with recognizing symptoms. Diagnosis can be made by taking a structured clinical history and meticulous perianal examination with rectal exam. Anorectal disorders can be effectively treated in general practice with primarily conservative measures like improving life style, toilet habits and pelvic physiotherapy. Symptoms can further be relieved by correct anal hygiene and topical ointments. Follow up is essential to evaluate response and adjust treatment. When results are insufficient patients can be referred to a gastroenterologist or gastrointestinal surgeon.

R. Loveikyte, M. Boer, C. N. van der Meulen, R. W. T. ter Steege, G. Tack, J. Kuyvenhoven, B. Jharap, M. K. Vu et al.

Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn’s and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn’s Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that—despite inconsistently measured iron parameters—is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care.

T. Straatmijer, Fiona D M van Schaik, A. Bodelier, M. Visschedijk, A. D. de Vries, C. Ponsioen, M. Pierik, A. V. van Bodegraven et al.

Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment.

A. Rezazadeh Ardabili, S. Jeuring, Z. Mujagic, L. Oostenbrug, M. Romberg-Camps, D. Jonkers, A. V. van Bodegraven, M. Pierik

our study concerning the long- term effectiveness and safety of thiopurine monotherapy in bowel the benefit– risk balance of thiopurines in real- practice and observed that thiopurine monotherapy durable for patients IBD, A reassuring prolonged effectiveness at 5 and 10 years after therapy

H. Cheng, Robert van Vorstenbosch, D. Pachen, L. W. Meulen, J. Straathof, J. Dallinga, D. Jonkers, A. Masclee et al.

INTRODUCTION: Early detection of colorectal cancer (CRC) by screening programs is crucial because survival rates worsen at advanced stages. However, the currently used screening method, the fecal immunochemical test (FIT), suffers from a high number of false-positives and is insensitive for detecting advanced adenomas (AAs), resulting in false-negatives for these premalignant lesions. Therefore, more accurate, noninvasive screening tools are needed. In this study, the utility of analyzing volatile organic compounds (VOCs) in exhaled breath in a FIT-positive population to detect the presence of colorectal neoplasia was studied. METHODS: In this multicenter prospective study, breath samples were collected from 382 FIT-positive patients with subsequent colonoscopy participating in the national Dutch bowel screening program (n = 84 negative controls, n = 130 non-AAs, n = 138 AAs, and n = 30 CRCs). Precolonoscopy exhaled VOCs were analyzed using thermal desorption-gas chromatography-mass spectrometry, and the data were preprocessed and analyzed using machine learning techniques. RESULTS: Using 10 discriminatory VOCs, AAs could be distinguished from negative controls with a sensitivity and specificity of 79% and 70%, respectively. Based on this biomarker profile, CRC and AA combined could be discriminated from controls with a sensitivity and specificity of 77% and 70%, respectively, and CRC alone could be discriminated from controls with a sensitivity and specificity of 80% and 70%, respectively. Moreover, the feasibility to discriminate non-AAs from controls and AAs was shown. DISCUSSION: VOCs in exhaled breath can detect the presence of AAs and CRC in a CRC screening population and may improve CRC screening in the future.

A. Rezazadeh Ardabili, S. Jeuring, Z. Mujagic, L. Oostenbrug, M. Romberg-Camps, D. Jonkers, A. V. van Bodegraven, M. Pierik

Thiopurines remain recommended as maintenance therapy in patients with inflammatory bowel disease (IBD). Despite their widespread use, long‐term effectiveness data are sparse and safety is an increasingly debated topic which thwarts proper delineation in the current IBD treatment algorithm.

A. R. Ardabili, L. Janssen, M. Romberg-Camps, D. Keszthelyi, D. Jonkers, A. A. V. Bodegraven, M. Pierik, Z. Mujagic

Marlijne C G de Graaf, C. Spooren, E. Hendrix, M. Hesselink, E. Feskens, A. Smolinska, D. Keszthelyi, M. Pierik et al.

Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) share common culprit foods and potential pathophysiological factors. However, how diet may contribute to disease course and whether this differs between both entities is unclear. We therefore investigated the association of dietary indices with intestinal inflammation and gastrointestinal symptoms in both IBD and IBS patients. Food frequency questionnaires from 238 IBD, 261 IBS and 195 healthy controls (HC) were available to calculate the overall diet quality by the Dutch Healthy Diet-Index 2015 (DHD-2015) and its inflammatory potential by the Adapted Dietary Inflammatory Index (ADII). Intestinal inflammation and symptoms were evaluated by faecal calprotectin and the Gastrointestinal Symptom Rating Scale, respectively. The DHD-2015 was lower in IBD and IBS versus HC (p < 0.001), being associated with calprotectin levels in IBD (b = −4.009, p = 0.006), and with abdominal pain (b = −0.012, p = 0.023) and reflux syndrome (b = −0.016, p = 0.004) in IBS. ADII scores were comparable between groups and were only associated with abdominal pain in IBD (b = 0.194, p = 0.004). In this side-by-side comparison, we found a lower diet quality that was differentially associated with disease characteristics in IBD versus IBS patients. Longitudinal studies are needed to further investigate the role of dietary factors in the development of flares and predominant symptoms.

T. Straatmijer, V. Biemans, M. Visschedijk, F. Hoentjen, A. D. de Vries, A. V. van Bodegraven, A. Bodelier, N. D. de Boer et al.

Z. Mujagic, M. Kasapi, D. Jonkers, I. García-Pérez, L. Vork, Z. Z. Weerts, J. Serrano-Contreras, A. Zhernakova et al.

ABSTRACT To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS), several modalities of biological and clinical data must be combined. We aimed to identify profiles of fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal metabolites were measured using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gut microbiome using shotgun metagenomic sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HCs) with extensive clinical, biological and phenotype information. Data were analyzed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome–metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on fecal microbiome–metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome–metabolome signatures for IBS, associated with altered serotonin metabolism and unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.

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