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Article ; Online: A comprehensive metabolite fingerprint of fibrostenosis in patients with Crohn’s disease

Simon Bos / Triana Lobatón / Martine De Vos / Sophie Van Welden / Vera Plekhova / Ellen De Paepe / Lynn Vanhaecke / Debby Laukens

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 11

Abstract: Abstract Intestinal fibrostenosis in patients with Crohn’s disease (CD) is a common and untreatable comorbidity that is notoriously difficult to monitor. We aimed to find metabolites associated with the presence of fibrostenosis in patients with CD using ...

Abstract	Abstract Intestinal fibrostenosis in patients with Crohn’s disease (CD) is a common and untreatable comorbidity that is notoriously difficult to monitor. We aimed to find metabolites associated with the presence of fibrostenosis in patients with CD using targeted and untargeted metabolomics analyses of serum and primary cell cultures using hyphenated ultra-high performance liquid chromatography high-resolution mass spectrometry. Targeted metabolomics revealed 11 discriminating metabolites in serum, which were enriched within the arginine and proline metabolism pathway. Based on untargeted metabolomics and discriminant analysis, 166 components showed a high predictive value. In addition, human intestinal fibroblasts isolated from stenotic tissue were characterized by differential levels of medium-chain dicarboxylic acids, which are proposed as an energy source through beta-oxidation, when oxidative phosphorylation is insufficient. Another energy providing pathway in such situations is anaerobic glycolysis, a theory supported by increased expression of hexokinase 2 and solute carrier family 16 member 1 in stenotic fibroblasts. Of interest, four (unannotated) metabolic components showed a negative correlation with hexokinase 2 gene expression. Together, this study provides a discriminative metabolic fingerprint in the serum and in intestinal fibroblasts of stenotic and non-stenotic patients with CD suggestive for increased production of building blocks for collagen synthesis and increased glycolysis.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-Term Environmental Hypoxia Exposure and Haematopoietic Prolyl Hydroxylase-1 Deletion Do Not Impact Experimental Crohn’s Like Ileitis

Cara De Galan / Martine De Vos / Pieter Hindryckx / Debby Laukens / Sophie Van Welden

Biology, Vol 10, Iss 887, p

2021 Volume 887

Abstract: Environmental hypoxia and hypoxia-induced signalling in the gut influence inflammatory bowel disease pathogenesis, however data is limited to colitis. Hence, we investigated the effect of environmental hypoxia and immune cell-specific deletion of oxygen ... ...

Abstract	Environmental hypoxia and hypoxia-induced signalling in the gut influence inflammatory bowel disease pathogenesis, however data is limited to colitis. Hence, we investigated the effect of environmental hypoxia and immune cell-specific deletion of oxygen sensor prolyl hydroxylase (PHD) 1 in a Crohn’s like ileitis mouse model. Therefore, 5-week-old C57/BL6 TNF ∆ARE/+ mice and wildtype (WT) littermates were housed in normoxia (21% O 2 ) or hypoxia (8% O 2 ) for 10 weeks. Systemic inflammation was assessed by haematology. Distal ileal hypoxia was evaluated by pimonidazole staining. The ileitis degree was scored on histology, characterized via qPCR and validated in haematopoietic Phd1-deficient TNF ∆ARE/+ mice. Our results demonstrated that hypoxia did not impact body weight evolution in WT and TNF ∆ARE/+ mice. Hypoxia increased red blood cell count, haemoglobin, haematocrit and increased pimonidazole intensity in the ileum. Interestingly, hypoxia evoked an increase in circulatory monocytes, ileal mononuclear phagocytes and proinflammatory cytokine expression in WT mice. Despite these alterations, no histological or ileal gene expression differences could be identified between TNF ∆ARE/+ mice housed in hypoxia versus normoxia nor between haematopoietic Phd1-deficient TNF ∆ARE/+ and their WT counterparts. Therefore, we demonstrated for the first time that long-term environmental hypoxia or haematopoietic Phd1-deletion does not impact experimental ileitis development.
Keywords	Ileal hypoxia ; TNF ∆ARE/+ mice ; prolyl hydroxylase 1 ; immune cell-specific ; hypoxia-induced signalling pathways ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prevalence of Fatigue and Unrecognized Depression in Patients with Inflammatory Bowel Disease in Remission under Immunosuppressants and Biologicals

Marie Truyens / Elodie De Ruyck / Gerard Bryan Gonzales / Simon Bos / Debby Laukens / Martine De Vos

Journal of Clinical Medicine, Vol 10, Iss 4107, p

2021 Volume 4107

Abstract: Background: Although highly prevalent among inflammatory bowel disease (IBD) patients, fatigue remains an unmet clinical need. The aim was to describe the prevalence of fatigue in an IBD population in remission and identify factors associated with ... ...

Abstract	Background: Although highly prevalent among inflammatory bowel disease (IBD) patients, fatigue remains an unmet clinical need. The aim was to describe the prevalence of fatigue in an IBD population in remission and identify factors associated with fatigue. Methods: IBD patients in clinical and biochemical remission under treatment with immunomodulators or biologicals were included. Fatigue, physical tiredness and depression were assessed using the fatigue Visual Analogue Scale (fVAS), the Shortened Fatigue Questionnaire (SFQ) and the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), respectively. Relevant clinical and biochemical parameters were included in regression analyses to identify factors associated with physical fatigue. Results: In total, 157 IBD patients were included. Up to 45.9% of patients reported fatigue, physical tiredness was observed in 51% and depression in 10.8%. The majority of patients with subclinical depression were fatigued. Female sex (OR = 4.17 [1.55–6.78], p = 0.002) was independently associated with physical fatigue. Transferrin saturation (OR = −0.11 [−0.22–−0.007], p = 0.037) and treatment with adalimumab (compared to infliximab, OR = −3.65 [−7.21–−0.08], p = 0.045) entailed a lower risk of fatigue. Conclusion: Fatigue is observed in about half of IBD patients in remission and can be a symptom of underlying undetected depression. Sex, transferrin saturation and medication were identified as independent risk factors.
Keywords	Crohn’s disease ; ulcerative colitis ; behavior ; depression ; NOD2 ; Lipocalin-2 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Role of integrin expression in the prediction of response to vedolizumab

Cara De Galan / Gerard Bryan Gonzales / Sophie Van Welden / Simon Jan Tavernier / Triana Lobaton / Wouter Van Moerkercke / Beatrijs Strubbe / Harald Peeters / Elisabeth Macken / Martine De Vos / Debby Laukens / Pieter Hindryckx

Clinical and Translational Medicine, Vol 12, Iss 4, Pp n/a-n/a (2022)

A prospective real‐life multicentre cohort study

2022

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The role of albumin and the extracellular matrix on the pathophysiology of oedema formation in severe malnutrition

Gerard Bryan Gonzales / James M. Njunge / Bonface M Gichuki / Bijun Wen / Moses Ngari / Isabel Potani / Johnstone Thitiri / Debby Laukens / Wieger Voskuijl / Robert Bandsma / Jill Vanmassenhove / James A Berkley

EBioMedicine, Vol 79, Iss , Pp 103991- (2022)

2022

Abstract: Summary: Background: While fluid flows in a steady state from plasma, through interstitium, and into the lymph compartment, altered fluid distribution and oedema can result from abnormal Starling's forces, increased endothelial permeability or impaired ... ...

Abstract	Summary: Background: While fluid flows in a steady state from plasma, through interstitium, and into the lymph compartment, altered fluid distribution and oedema can result from abnormal Starling's forces, increased endothelial permeability or impaired lymphatic drainage. The mechanism of oedema formation, especially the primary role of hypoalbuminaemia, remains controversial. Here, we explored the roles of albumin and albumin-independent mechanisms in oedema formation among children with severe malnutrition (SM). Methods: We performed secondary analysis of data obtained from two independent clinical trials in Malawi and Kenya (NCT02246296 and NCT00934492). We then used an unconventional strategy of comparing children with kwashiorkor and marasmus by matching (discovery cohort, n = 144) and normalising (validation cohort, n = 98, 2 time points) for serum albumin. Untargeted proteomics was used in the discovery cohort to determine plausible albumin-independent mechanisms associated with oedema, which was validated using enzyme-linked immunosorbent assay and multiplex assays in the validation cohort. Findings: We demonstrated that low serum albumin is necessary but not sufficient to develop oedema in SM. We further found that markers of extracellular matrix (ECM) degradation rather than markers of EG degradation distinguished oedematous and non-oedematous children with SM. Interpretation: Our results show that oedema formation has both albumin-dependent and independent mechanisms. ECM integrity appears to have a greater role in oedema formation than EG shedding in SM. Funding: Research Foundation Flanders (FWO), Thrasher Foundation (15122 and 9403), VLIR-UOS-Ghent University Global Minds Fund, Bill & Melinda Gates Foundation (OPP1131320), MRC/DfID/Wellcome Trust Global Health Trials Scheme (MR/M007367/1), Canadian Institutes of Health Research (156307), Wellcome Trust (WT083579MA).
Keywords	Starling forces ; Extracellular matrix ; Endothelial glycocalyx ; Oedema ; Proteomics ; Severe malnutrition ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	360
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The quorum sensing peptide EntF* promotes colorectal cancer metastasis in mice

Evelien Wynendaele / Nathan Debunne / Yorick Janssens / Anton De Spiegeleer / Frederick Verbeke / Liesa Tack / Sophie Van Welden / Evy Goossens / Daniel Knappe / Ralf Hoffmann / Christophe Van De Wiele / Debby Laukens / Peter Van Eenoo / Lars Vereecke / Filip Van Immerseel / Olivier De Wever / Bart De Spiegeleer

BMC Biology, Vol 20, Iss 1, Pp 1-

a new factor in the host-microbiome interaction

2022 Volume 16

Abstract: Abstract Background Colorectal cancer, one of the most common malignancies worldwide, is associated with a high mortality rate, mainly caused by metastasis. Comparative metagenome-wide association analyses of healthy individuals and cancer patients ... ...

Abstract	Abstract Background Colorectal cancer, one of the most common malignancies worldwide, is associated with a high mortality rate, mainly caused by metastasis. Comparative metagenome-wide association analyses of healthy individuals and cancer patients suggest a role for the human intestinal microbiota in tumor progression. However, the microbial molecules involved in host-microbe communication are largely unknown, with current studies mainly focusing on short-chain fatty acids and amino acid metabolites as potential mediators. Quorum sensing peptides are not yet considered in this context since their presence in vivo and their ability to affect host cells have not been reported so far. Results Here, we show that EntF, a metabolite of the quorum sensing peptide EntF produced by Enterococcus faecium, is naturally present in mice bloodstream. Moreover, by using an orthotopic mouse model, we show that EntF promotes colorectal cancer metastasis in vivo, with metastatic lesions in liver and lung tissues. In vitro tests suggest that EntF* regulates E-cadherin expression and consequently the epithelial-mesenchymal transition, via the CXCR4 receptor. In addition, alanine-scanning analysis indicates that the first, second, sixth, and tenth amino acid of EntF* are critical for epithelial-mesenchymal transition and tumor metastasis. Conclusion Our work identifies a new class of molecules, quorum sensing peptides, as potential regulators of host-microbe interactions. We prove, for the first time, the presence of a selected quorum sensing peptide metabolite in a mouse model, and we demonstrate its effects on colorectal cancer metastasis. We believe that our work represents a starting point for future investigations on the role of microbiome in colorectal cancer metastasis and for the development of novel bio-therapeutics in other disease areas.
Keywords	Quorum sensing peptides ; Microbiota ; Colorectal cancer metastasis ; Orthotopic mice model ; LC-MS ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Evidence for a Potential Role of Metallothioneins in Inflammatory Bowel Diseases

Debby Laukens / Anouk Waeytens / Martine De Vos

Mediators of Inflammation, Vol

2009 Volume 2009

Keywords	Pathology ; RB1-214 ; Medicine ; R ; DOAJ:Pathology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Language	English
Publishing date	2009-01-01T00:00:00Z
Publisher	Hindawi Publishing Corporation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Translational research into the effects of cigarette smoke on inflammatory mediators and epithelial TRPV1 in Crohn's disease.

Liesbeth Allais / Stephanie Verschuere / Tania Maes / Rebecca De Smet / Sarah Devriese / Gerard Bryan Gonzales / Harald Peeters / Koen Van Crombruggen / Claus Bachert / Martine De Vos / Guy G Brusselle / Ken R Bracke / Claude A Cuvelier / Debby Laukens

PLoS ONE, Vol 15, Iss 8, p e

2020 Volume 0236657

Abstract: Crohn's disease is a pathological condition of the gastro-intestinal tract, causing severe transmural inflammation in the ileum and/or colon. Cigarette smoking is one of the best known environmental risk factors for the development of Crohn's disease. ... ...

Abstract	Crohn's disease is a pathological condition of the gastro-intestinal tract, causing severe transmural inflammation in the ileum and/or colon. Cigarette smoking is one of the best known environmental risk factors for the development of Crohn's disease. Nevertheless, very little is known about the effect of prolonged cigarette smoke exposure on inflammatory modulators in the gut. We examined the effect of cigarette smoke on cytokine profiles in the healthy and inflamed gut of human subjects and in the trinitrobenzene sulphonic acid mouse model, which mimics distal Crohn-like colitis. In addition, the effect of cigarette smoke on epithelial expression of transient receptor potential channels and their concurrent increase with cigarette smoke-augmented cytokine production was investigated. Active smoking was associated with increased IL-8 transcription in ileum of controls (p < 0,001; n = 18-20/group). In the ileum, TRPV1 mRNA levels were decreased in never smoking Crohn's disease patients compared to healthy subjects (p <0,001; n = 20/group). In the colon, TRPV1 mRNA levels were decreased (p = 0,046) in smoking healthy controls (n = 20/group). Likewise, healthy mice chronically exposed to cigarette smoke (n = 10/group) showed elevated ileal Cxcl2 (p = 0,0075) and colonic Kc mRNA levels (p = 0,0186), whereas TRPV1 mRNA and protein levels were elevated in the ileum (p = 0,0315). Although cigarette smoke exposure prior to trinitrobenzene sulphonic acid administration did not alter disease activity, increased pro-inflammatory cytokine production was observed in the distal colon (Kc: p = 0,0273; Cxcl2: p = 0,104; Il1-β: p = 0,0796), in parallel with the increase of Trpv1 mRNA (p < 0,001). We infer that CS affects pro-inflammatory cytokine expression in healthy and inflamed gut, and that the simultaneous modulation of TRPV1 may point to a potential involvement of TRPV1 in cigarette smoke-induced production of inflammatory mediators.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Butyrate-producing bacteria supplemented in vitro to Crohn’s disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity

Annelies Geirnaert / Marta Calatayud / Charlotte Grootaert / Debby Laukens / Sarah Devriese / Guy Smagghe / Martine De Vos / Nico Boon / Tom Van de Wiele

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 14

Abstract: Abstract The management of the dysbiosed gut microbiota in inflammatory bowel diseases (IBD) is gaining more attention as a novel target to control this disease. Probiotic treatment with butyrate-producing bacteria has therapeutic potential since these ... ...

Abstract	Abstract The management of the dysbiosed gut microbiota in inflammatory bowel diseases (IBD) is gaining more attention as a novel target to control this disease. Probiotic treatment with butyrate-producing bacteria has therapeutic potential since these bacteria are depleted in IBD patients and butyrate has beneficial effects on epithelial barrier function and overall gut health. However, studies assessing the effect of probiotic supplementation on microbe-microbe and host-microbe interactions are rare. In this study, butyrate-producing bacteria (three mono-species and one multispecies mix) were supplemented to the fecal microbial communities of ten Crohn’s disease (CD) patients in an in vitro system simulating the mucus- and lumen-associated microbiota. Effects of supplementation in short-chain fatty acid levels, bacterial colonization of mucus environment and intestinal epithelial barrier function were evaluated. Treatment with F. prausnitzii and the mix of six butyrate-producers significantly increased the butyrate production by 5–11 mol%, and colonization capacity in mucus- and lumen-associated CD microbiota. Treatments with B. pullicaecorum 25-3T and the mix of six butyrate-producers improved epithelial barrier integrity in vitro. This study provides proof-of-concept data for the therapeutic potential of butyrate-producing bacteria in CD and supports the future preclinical development of a probiotic product containing butyrate-producing species.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Involvement of endoplasmic reticulum stress in inflammatory bowel disease

Sara Bogaert / Martine De Vos / Kim Olievier / Harald Peeters / Dirk Elewaut / Bart Lambrecht / Philippe Pouliot / Debby Laukens

PLoS ONE, Vol 6, Iss 10, p e

a different implication for colonic and ileal disease?

2011 Volume 25589

Abstract: BACKGROUND: Endoplasmic reticulum (ER) stress has been suggested to play a role in inflammatory bowel disease (IBD). The three branches (ATF6, IRE1 and PERK) of the unfolded protein response (UPR) have different roles and are not necessarily activated ... ...

Abstract	BACKGROUND: Endoplasmic reticulum (ER) stress has been suggested to play a role in inflammatory bowel disease (IBD). The three branches (ATF6, IRE1 and PERK) of the unfolded protein response (UPR) have different roles and are not necessarily activated simultaneously. METHODOLOGY/PRINCIPAL FINDINGS: Expression of UPR-related genes was investigated in colonic and ileal biopsies of 23 controls, 15 ulcerative colitis (UC) and 54 Crohn's disease (CD) patients. This expression was confirmed at protein level in colonic and ileal samples of five controls, UC and CD patients. HSPA5, PDIA4 and XBP1s were significantly increased in colonic IBD at mRNA and/or protein levels, indicating activation of the ATF6 and IRE1 branch. Colonic IBD was associated with increased phosphorylation of EIF2A suggesting the activation of the PERK branch, but subsequent induction of GADD34 was not observed. In ileal CD, no differential expression of the UPR-related genes was observed, but our data suggested a higher basal activation of the UPR in the ileal mucosa of controls. This was confirmed by the increased expression of 16 UPR-related genes as 12 of them were significantly more expressed in ileal controls compared to colonic controls. Tunicamycin stimulation of colonic and ileal samples of healthy individuals revealed that although the ileal mucosa is exhibiting this higher basal UPR activation, it is still responsive to ER stress, even more than colonic mucosa. CONCLUSIONS/SIGNIFICANCE: Activation of the three UPR-related arms is seen in colonic IBD-associated inflammation. However, despite EIF2A activation, inflamed colonic tissue did not increase GADD34 expression, which is usually involved in re-establishment of ER homeostasis. This study also implies the presence of a constitutive UPR activation in healthy ileal mucosa, with no further activation during inflammation. Therefore, engagement of the UPR differs between colon and ileum and this could be a factor in the development of ileal or colonic disease.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2011-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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