Tu1760 Functional Evidence for a Causative Role of the Intestinal Microbiota in Crohn's Disease-Like Ileitis Using Antibiotic-Treated and Germ-Free TNFDeltaare/+ Mice

2014 ◽  
Vol 146 (5) ◽  
pp. S-836
Author(s):  
Monika Schaubeck ◽  
Thomas Clavel ◽  
Nadine Waldschmitt ◽  
Jan Wehkamp ◽  
Ines Martinez ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Microbiota ◽  
Causative Role ◽  
Germ Free ◽  
Tnfdeltaare Mice

scholarly journals Mycobacterium Avium Paratuberculosisand the Etiology of Crohn’s Disease: A Review of the Controversy from the Clinician’s Perspective

2010 ◽  
Vol 24 (10) ◽  
pp. 619-624 ◽  
Author(s):  
Greg Rosenfeld ◽  
Brian Bressler
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mycobacterium Avium ◽  
Immunosuppressive Agents ◽  
Infectious Agent ◽  
Causative Role ◽  
Mycobacterium Avium Paratuberculosis ◽  
Considerable Research ◽  
Chronic Inflammatory Condition

Mycobacterium avium paratuberculosis(MAP) is an obligate intracellular organism that has frequently been associated with Crohn’s disease (CD). Because CD is a chronic inflammatory condition, many researchers have speculated that an infectious agent must be the cause of CD. MAP has often been proposed to be one such agent; however, despite considerable research, the evidence remains inconclusive. Higher levels of MAP have been found in the tissues and blood of CD patients than in controls, forming the foundation for much of the research into the role of MAP in CD and the primary argument in support of a causative role for MAP in CD. MAP is a slow-growing and fastidious organism that is difficult to grow in culture and, therefore, challenging to detect in patients. As a result, there has been variability in the results of studies attempting to detect the presence of MAP in CD patients, and considerable controversy over whether this organism has a causative role in the etiology of CD. Two main hypotheses exist with respect to the role of MAP in CD. The first is that MAP is a principal cause of CD, while the second is that MAP is more prevalent because of the immune dysfunction seen in CD but does not play a causative role. Clinicians are often faced with questions regarding the role of this organism and the need to treat it. The present article attempts to provide an overview of the controversy including the nature of the mycobacterium, the difficulty in detecting it, the use of antimycobacterial agents to treat it and the effect of immunosuppressive agents – all from a clinician’s perspective. Although the role of MAP in CD remains controversial and an area of considerable research, it is currently only of academic interest because there is no clinically useful test to identify the presence of the organism, and no evidence to support the use of antibiotics to eradicate it for the treatment of CD.

P056 DISCRIMINATORY ROLE OF ANTI-MICROBIAL ANTIBODIES IN DIAGNOSIS OF CROHN'S DISEASE AGAINST NORMAL AND OTHER MIMICS

2020 ◽  
Vol 158 (3) ◽  
pp. S21-S22
Author(s):  
Peilin Zhang ◽  
Lawrence Minardi ◽  
J. Todd Kuenstner ◽  
Steve Zekan ◽  
Rusty Kruzelock
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease

THE EVALUATION OF SERUM SEROTONIN LEVEL AMONG PATIENTS WITH CROHN’S DISEASE AND ITS IMPACT ON QUALITY OF LIFE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S55-S55
Author(s):  
Marcin Sochal ◽  
Piotr Bialasiewicz ◽  
Agata Gabryelska ◽  
Renata Talar-Wojnarowska ◽  
Jakub Fichna ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Sleep Quality ◽  
Sleep Fragmentation ◽  
Clinical Severity ◽  
Serotonin Level ◽  
Intestinal Physiology ◽  
Tnf Α

Abstract Background and aims Serotonin affects intestinal physiology, mood, as well as circadian rhythm. Moreover, serotonin has proinflammatory function. Therefore, the aim of this study was to investigate the role of serotonin in clinical severity of Crohn’s Disease (CD) and its effect on pain and sleep quality. Methods Fifty-nine CD patients (34 in exacerbation and 25 in remission according to the Harvey-Bradshaw Index-HBI) and 25 health control individuals(HC) were recruited. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) and subjective severity of pain by the Visual Analog Scale (VAS). Seventeen patients were treated with anti-TNF-α induction therapy for 14 weeks. Results Serotonin level was higher in CD (145.12ng/mL, IQR:98.14–179.25) compared to HC (87.52ng/mL, IQR:70.04–129.39; p=0.002) and in exacerbation of CD (157.66ng/mL, IQR:111.94–197.64) compared to remission (122.33ng/mL, IQR:83.28–163.67; p=0.029). Serotonin level with cut-off point of 92.45 ng/mL is useful for distinguishing participants with CD from HC (sensitivity: 78%, specificity: 60%, positive predictive value: 82%). Positive correlation between serotonin and HBI (r=0.279, p=0.032) and severity of diarrhoea (r=0.260, p=0.047) were found. Serotonin does not correlate with PSQI (r=0.152, p=0.168), but correlates with presence of sleep fragmentation for example by getting up to use the bathroom (joined 5b-5j PSQI questions; r=0.270, p=0.039). Correlations between serotonin and VAS were also obtained (r=0.220, p=0.045). Moreover, serotonin level significantly decreased after anti-TNF-α therapy (192.35ng/mL, IQR:150.36–225.56 vs. 121.11ng/mL, IQR:91.28–188.87; p=0.006). The study was funded by National Science Centre, Poland (#2018/31/N/NZ5/03715). Conclusions Serotonin level correlates with the severity of CD and decreases after anti-TNF-α therapy. It is associated with sleep fragmentation, which may be caused by diarrhea.

scholarly journals The role of epigenetic modifications for the pathogenesis of Crohn's disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
M. Hornschuh ◽  
E. Wirthgen ◽  
M. Wolfien ◽  
K. P. Singh ◽  
O. Wolkenhauer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Biomarkers ◽  
Insight Into ◽  
Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

scholarly journals Antagonism of Adherent Invasive E. coli LF82 With Human α-defensin 5 in the Follicle-associated Epithelium of Patients With Ileal Crohn’s Disease

2020 ◽  
Author(s):  
Lina Y Alkaissi ◽  
Martin E Winberg ◽  
Stéphanie DS Heil ◽  
Staffan Haapaniemi ◽  
Pär Myrelid ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ex Vivo ◽  
Ussing Chambers ◽  
E Coli ◽  
Follicle Associated Epithelium ◽  
Vitro Model ◽  
Set Up

Abstract Background The first visible signs of Crohn’s disease (CD) are microscopic erosions over the follicle-associated epithelium (FAE). The aim of the study was to investigate the effects of human α-defensin 5 (HD5) on adherent-invasive Escherichia coli LF82 translocation and HD5 secretion after LF82 exposure in an in vitro model of human FAE and in human FAE ex vivo. Methods An in vitro FAE-model was set up by the coculture of Raji B cells and Caco-2-cl1 cells. Ileal FAE from patients with CD and controls were mounted in Ussing chambers. The effect of HD5 on LF82 translocation was studied by LF82 exposure to the cells or tissues with or without incubation with HD5. The HD5 secretion was measured in human FAE exposed to LF82 or Salmonella typhimurium. The HD5 levels were evaluated by immunofluorescence, immunoblotting, and ELISA. Results There was an increased LF82 translocation across the FAE-model compared with Caco-2-cl1 (P < 0.05). Incubation of cell/tissues with HD5 before LF82 exposure reduced bacterial passage in both models. Human FAE showed increased LF82 translocation in CD compared with controls and attenuated passage after incubation with sublethal HD5 in both CD and controls (P < 0.05). LF82 exposure resulted in a lower HD5 secretion in CD FAE compared with controls (P < 0.05), whereas Salmonella exposure caused equal secretion on CD and controls. There were significantly lower HD5 levels in CD tissues compared with controls. Conclusions Sublethal HD5 reduces the ability of LF82 to translocate through FAE. The HD5 is secreted less in CD in response to LF82, despite a normal response to Salmonella. This further implicates the integrated role of antimicrobial factors and barrier function in CD pathogenesis.

scholarly journals Evaluation of changes in intestinal microbiota in Crohn’s disease patients after anti-TNF alpha treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Sanchis-Artero ◽  
Juan Francisco Martínez-Blanch ◽  
Sergio Manresa-Vera ◽  
Ernesto Cortés-Castell ◽  
Marina Valls-Gandia ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Microbiota ◽  
Area Under The Curve ◽  
Alpha Diversity ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Multicenter Observational Study ◽  
Partial Restoration ◽  
Before And After

AbstractIntestinal dysbiosis is key in the onset and development of Crohn’s disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and non-responders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.

scholarly journals Role of Probiotics and Their Metabolites in Inflammatory Bowel Diseases (IBDs)

2021 ◽  
Vol 12 (1) ◽  
pp. 56-66
Author(s):  
Toumi Ryma ◽  
Arezki Samer ◽  
Imene Soufli ◽  
Hayet Rafa ◽  
Chafia Touil-Boukoffa
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Clinical Symptoms ◽  
Therapeutic Potential ◽  
Short Chain Fatty Acids ◽  
Active Metabolites ◽  
Complex Disorders ◽  
Inflammatory Bowel

Inflammatory Bowel Disease (IBD) is a term used to describe a group of complex disorders of the gastrointestinal (GI) tract. IBDs include two main forms: Crohn’s Disease (CD) and Ulcerative Colitis (UC), which share similar clinical symptoms but differ in the anatomical distribution of the inflammatory lesions. The etiology of IBDs is undetermined. Several hypotheses suggest that Crohn’s Disease and Ulcerative Colitis result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. While there is no cure for IBDs, most common treatments (medication and surgery) aim to reduce inflammation and help patients to achieve remission. There is growing evidence and focus on the prophylactic and therapeutic potential of probiotics in IBDs. Probiotics are live microorganisms that regulate the mucosal immune system, the gut microbiota and the production of active metabolites such as Short-Chain Fatty Acids (SCFAs). This review will focus on the role of intestinal dysbiosis in the immunopathogenesis of IBDs and understanding the health-promoting effects of probiotics and their metabolites.

scholarly journals The multiple faces of inflammatory enteric glial cells: is Crohn’s disease a gliopathy?

2018 ◽  
Vol 315 (1) ◽  
pp. G1-G11 ◽  
Author(s):  
Camille Pochard ◽  
Sabrina Coquenlorge ◽  
Marie Freyssinet ◽  
Philippe Naveilhan ◽  
Arnaud Bourreille ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Glial Cells ◽  
Physiological Role ◽  
Enteric Neurons ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Enteric Glial Cells ◽  
Glial Reactivity

Gone are the days when enteric glial cells (EGC) were considered merely satellites of enteric neurons. Like their brain counterpart astrocytes, EGC express an impressive number of receptors for neurotransmitters and intercellular messengers, thereby contributing to neuroprotection and to the regulation of neuronal activity. EGC also produce different soluble factors that regulate neighboring cells, among which are intestinal epithelial cells. A better understanding of EGC response to an inflammatory environment, often referred to as enteric glial reactivity, could help define the physiological role of EGC and the importance of this reactivity in maintaining gut functions. In chronic inflammatory disorders of the gut such as Crohn’s disease (CD) and ulcerative colitis, EGC exhibit abnormal phenotypes, and their neighboring cells are dysfunctional; however, it remains unclear whether EGC are only passive bystanders or active players in the pathophysiology of both disorders. The aim of the present study is to review the physiological roles and properties of EGC, their response to inflammation, and their role in the regulation of the intestinal epithelial barrier and to discuss the emerging concept of CD as an enteric gliopathy.

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