Immunolocalization of leptin and leptin receptor in colorectal mucosa of ulcerative colitis, Crohn’s disease and control subjects with no inflammatory bowel disease

Abstract The expression of leptin and leptin receptor (Ob-R) has been partially elucidated in colon of patients with inflammatory bowel diseases (IBDs), even though leptin is involved in angiogenesis and inflammation. We previously reported overexpression of GLUT5 fructose transporter, in aberrant clusters of lymphatic vessels in lamina propria of IBD and controls. Here, we examine leptin and Ob-R expression in the same biopsies. Specimens were obtained from patients with ulcerative colitis (UC), Crohn’s disease (CD) and controls who underwent screening for colorectal cancer, follow-up after polypectomy or with a history of lower gastrointestinal symptoms. Immunohistochemistry revealed leptin in apical and basolateral membranes of short epithelial portions, Ob-R on the apical pole of epithelial cells. Leptin and Ob-R were also identified in structures and cells scattered in the lamina propria. In UC, a significant correlation between leptin and Ob-R in the lamina propria was found in all inflamed samples, beyond non-inflamed samples of the proximal tract, while in CD, it was found in inflamed distal samples. Most of the leptin and Ob-R positive areas in the lamina propria were also GLUT5 immunoreactive in inflamed and non-inflamed mucosa. A significant correlation of leptin or Ob-R expression with GLUT5 was observed in the inflamed distal samples from UC. Our findings suggest that there are different sites of leptin and Ob-R expression in large intestine and those in lamina propria do not reflect the status of mucosal inflammation. The co-localization of leptin and/or Ob-R with GLUT5 may indicate concomitance effects in colorectal lamina propria areas.

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Prebiotics in inflammatory bowel diseases

British Journal Of Nutrition ◽

10.1017/s0007114507832958 ◽

2007 ◽

Vol 98 (S1) ◽

pp. S85-S89 ◽

Cited By ~ 33

Author(s):

Francisco Guarner

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Intestinal Bacteria ◽

Commensal Bacteria ◽

Mucosal Inflammation ◽

Microbial Composition ◽

Principal Mechanism ◽

Food Ingredients ◽

Inflammatory Bowel

In genetically susceptible individuals, an altered mucosal immune response against some commensal bacteria of the gut ecosystem appears to be the principal mechanism leading to intestinal lesions in inflammatory bowel disease (IBD). The information currently available does not provide an exact explanation about the origin of this important dysfunction of the interaction between host and commensal bacteria, but an altered microbial composition has been detected in the gut ecosystem of patients with Crohn's disease or ulcerative colitis. Prebiotics are food ingredients not digested nor absorbed in the upper intestinal tract that are fermented by intestinal bacteria in a selective way promoting changes in the gut ecosystem. Experimental and human studies have shown that inulin and oligofructose stimulate saccharolysis in the colonic lumen and favour the growth of indigenous lactobacilli and bifidobacteria. These effects are associated with reduced mucosal inflammation in animal models of IBD. Strong experimental evidence supports the hypothesis that inulin and oligofructose can offer an opportunity to prevent or mitigate intestinal inflammatory lesions in human Crohn's disease, ulcerative colitis, and pouchitis. Encouraging results have been obtained in preliminary clinical trials.

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Immunosppressive Agents in Inflammatory Bowel Disease: Current Status and Future Prospects

Canadian Journal of Gastroenterology ◽

10.1155/1994/580410 ◽

1994 ◽

Vol 8 (6) ◽

pp. 383-387

Author(s):

Fergus Shanahan ◽

Gerald C O'’Sullivan ◽

J Kevin Collins

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Tissue Injury ◽

Current Status ◽

Mucosal Inflammation ◽

Clinical Role ◽

Inflammatory Bowel

Inflammatory bowel disease involves an interaction between genetic susceptibility factors and environmental triggers, and the intestinal injury is mediated by the host immunoinflammatory response. Identification of the mechanisms and mediators that contribute to the tissue injury has provided a sound rationale for the therapeutic use of immunosuppressive and immunomodulatory agents. The efficacy of traditional immunosuppressive drugs, such as the purine analogues in both Crohn’s disease and ulcerative colitis, is well established. The major limitation of the use of these drugs is the delayed clinical response associated with their use. This has prompted an evaluation of other immunosuppressivcs, such as cyclosporine and related drugs, that have a more rapid onset of action. Convincing data indicate a distinct role for cyclosporine in certain patients with acute severe ulcerative colitis. However, despite early promising results with cyclosporine in Crohn’s disease, recent results have been less encouraging. There is also uncertainty about the exact clinical role of cyclosporine because of concerns regarding long term toxicity. At present, many investigators regard cyclosporine as an interim measure for acutely ill patients. The challenge that remains is the development of novel immunomodulatory strategies that are specific for the mucosal immune system and that are based on recent advances in our understanding of the pathogenesis of mucosal inflammation.

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Monocytes in Inflammatory Bowel Disease: Monocyte and Serum Lysosomal Enzyme Activity

Clinical Science ◽

10.1042/cs0580295 ◽

1980 ◽

Vol 58 (4) ◽

pp. 295-300 ◽

Cited By ~ 22

Author(s):

A. S. Mee ◽

D. P. Jewell

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Enzyme Activity ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Mucosal Inflammation ◽

Marker Enzyme ◽

Control Subjects ◽

Inflammatory Bowel

1. The activity of a specific lysosomal marker enzyme N'-acetyl-β-d-glucosaminidase has been determined fluorimetrically in the monocytes and in the serum of patients with Crohn's disease and ulcerative colitis and compared with results obtained from healthy and disease control subjects. 2. Enzyme activities were measured in a monocyte-enriched suspension from a Ficoll-Triosil gradient and in an adherent monocyte preparation. 3. The results indicate that enzyme activity is greater in both monocytes and sera of patients with Crohn's disease and ulcerative colitis than in those from control subjects (P0.01) 4. Enzyme activity within monocytes correlated with disease activity (P0.05) 5. Lysosomal enzymes may contribute to the pathogenesis of the mucosal inflammation in inflammatory bowel disease.

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Levels of Anti-Citrullinated Protein Antibodies and Rheumatoid Factor, Including IgA Isotypes, and Articular Manifestations in Ulcerative Colitis and Crohn’s Disease

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17218054 ◽

2020 ◽

Vol 17 (21) ◽

pp. 8054

Author(s):

Koen M. J. Janssen ◽

Hilde Hop ◽

Arjan Vissink ◽

Gerard Dijkstra ◽

Menke J. de Smit ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Rheumatoid Factor ◽

Healthy Subjects ◽

Immunoglobulin A ◽

Mucosal Inflammation ◽

Inflammatory Bowel ◽

Citrullinated Protein

Systemic presence of arthritis autoantibodies (AAb) is specific for rheumatoid arthritis (RA). AAb initiation might be triggered by chronic mucosal inflammation, such as in inflammatory bowel disease (IBD). We assessed the prevalence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in ulcerative colitis (UC) and Crohn’s disease (CD) patients, with regard to the prevalence of joint complaints in AAb+ versus AAb− IBD patients. RA patients and healthy subjects (HC) served as controls. Serum was collected from 226 UC, 165 CD and 86 RA patients, and 36 HCs. One-hundred-and-ten UC (48.7%) and 76 CD (46.1%) patients were seropositive for at least one autoantibody, compared to 4 (13.9%) HCs and 81 (94.2%) RA patients. Eighty-three (37%) UC and 52 (32%) CD patients were seropositive for the anti-cyclic citrullinated protein antibody (anti-CCP2) of the immunoglobulin A type (IgA anti-CCP2), compared to 1 (2.8%) HC and 64 (74%) RA patients. RF of the immunoglobulin G type (IgG RF) and IgA RF seropositivity in UC and CD patients was comparable to HCs and low compared to RA patients. Arthralgia was reported by 34 (18.7%) UC and 50 (33.1%) CD patients, but presence of arthralgia was not increased in AAb+ patients. AAbs are frequently present in IBD patients, supporting the hypothesis that inflammation of intestinal mucosa induces low systemic levels of ACPA.

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Can faecal calprotectin predict relapse in inflammatory bowel disease: a mini review

Frontline Gastroenterology ◽

10.1136/flgastro-2016-100686 ◽

2016 ◽

Vol 9 (1) ◽

pp. 23-28 ◽

Cited By ~ 5

Author(s):

T S Chew ◽

J C Mansfield

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Bowel Disease ◽

Calcium Binding ◽

Inflammatory Cells ◽

Mucosal Inflammation ◽

Faecal Calprotectin ◽

Inflammatory Bowel

Crohn's disease and ulcerative colitis are chronic inflammatory disorders affecting the gastrointestinal tract. Faecal calprotectin is a protein complex of the S-100 family of calcium-binding proteins present in inflammatory cells that can be measured in stool samples, which act as a biomarker for bowel inflammation. Elevated faecal calprotectin has been shown to reflect the presence of ongoing mucosal inflammation, which improves with mucosal healing. The aim of this review was to evaluate the available evidence on the ability of faecal calprotectin to predict a relapse in inflammatory bowel disease. Multiple retrospective studies have shown that patients who relapse have significantly higher levels of calprotectin in their stool compared with non-relapsers, especially in ulcerative colitis. Elevated faecal calprotectin postoperatively in Crohn's disease was also shown to be indicative of a relapse. However, the association of a raised faecal calprotectin and relapse is not universal and may be explained by the different patterns of mucosal inflammatory activity that exist. In conclusion, we put forward our hypothesis that changes such as a rise in faecal calprotectin levels may be more predictive of a relapse than absolute values.

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Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

Current Clinical Pharmacology ◽

10.2174/1574884715666200312100237 ◽

2020 ◽

Vol 15 (3) ◽

pp. 216-233 ◽

Cited By ~ 1

Author(s):

Maliha Naseer ◽

Shiva Poola ◽

Syed Ali ◽

Sami Samiullah ◽

Veysel Tahan

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Clinical Trials ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Adverse Effects ◽

Bowel Disease ◽

Relapse Prevention ◽

Remission Induction ◽

Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

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The Changing Prognosis of Ulcerative Colitis and Crohn’s Disease by Decades

Crohn's & Colitis 360 ◽

10.1093/crocol/otab008 ◽

2021 ◽

Author(s):

Burton I Korelitz ◽

Judy Schneider

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Medical Therapy ◽

Bowel Disease ◽

Surgical Intervention ◽

Inflammatory Bowel

Abstract We present a bird’s eye view of the prognosis for both ulcerative colitis and Crohn’s disease as contained in the database of an Inflammatory Bowel Disease gastroenterologist covering the period from 1950 until the present utilizing the variables of medical therapy, surgical intervention, complications and deaths by decades.

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Targeted 1H NMR metabolomics and immunological phenotyping of human fresh blood and serum samples discriminate between healthy individuals and inflammatory bowel disease patients treated with anti-TNF

Journal of Molecular Medicine ◽

10.1007/s00109-021-02094-y ◽

2021 ◽

Author(s):

Sara Notararigo ◽

Manuel Martín-Pastor ◽

Juan E. Viñuela Roldán ◽

Adriano Quiroga ◽

J. Enrique Dominguez-Munoz ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Clinical Practice ◽

Crohn's Disease ◽

T Lymphocyte ◽

Fresh Blood ◽

Serum Samples ◽

Nmr Metabolomics ◽

Inflammatory Bowel

Abstract Inflammatory bowel disease is a multifactorial etiology, associated with environmental factors that can trigger both debut and relapses. A high level of tumor necrosis factor-α in the gut is the main consequence of immune system imbalance. The aim of treatment is to restore gut homeostasis. In this study, fresh blood and serum samples were used to identify biomarkers and to discriminate between Crohn’s disease and ulcerative colitis patients under remission treated with anti-TNF. Metabolomics based on Nuclear Magnetic Resonance spectroscopy (NMR) was used to detect unique biomarkers for each class of patients. Blood T lymphocyte repertories were characterized, as well as cytokine and transcription factor profiling, to complement the metabolomics data. Higher levels of homoserine-methionine and isobutyrate were identified as biomarkers of Crohn’s disease with ileocolic localization. For ulcerative colitis, lower levels of creatine-creatinine, proline, and tryptophan were found that reflect a deficit in the absorption of essential amino acids in the gut. T lymphocyte phenotyping and its functional profiling revealed that the overall inflammation was lower in Crohn’s disease patients than in those with ulcerative colitis. These results demonstrated that NMR metabolomics could be introduced as a high-throughput evaluation method in routine clinical practice to stratify both types of patients related to their pathology. Key messages NMR metabolomics is a non-invasive tool that could be implemented in the normal clinical practice for IBD to assess beneficial effect of the treatment. NMR metabolomics is a useful tool for precision medicine, in order to sew a specific treatment to a specific group of patients. Finding predictors of response to IFX would be desirable to select patients affected by IBD. Immunological status of inflammations correlates with NMR metabolomics biomarkers.

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

Gastroenterology Insights ◽

10.3390/gastroent12010006 ◽

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.

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Inflammatory Bowel Disease: An Overview of Immune Mechanisms and Biological Treatments

Mediators of Inflammation ◽

10.1155/2015/493012 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 69

Author(s):

Bruno Rafael Ramos de Mattos ◽

Maellin Pereira Gracindo Garcia ◽

Julia Bier Nogueira ◽

Lisiery Negrini Paiatto ◽

Cassia Galdino Albuquerque ◽

...

Keyword(s):

Ulcerative Colitis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Severe Disease ◽

Biological Therapies ◽

Promising Alternative ◽

Biological Treatments ◽

Bowel Diseases ◽

Inflammatory Bowel ◽

And Behavior

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the intestinal tract associated with an imbalance of the intestinal microbiota. Crohn’s disease (CD) and ulcerative colitis (UC) are the most widely known types of IBD and have been the focus of attention due to their increasing incidence. Recent studies have pointed out genes associated with IBD susceptibility that, together with environment factors, may contribute to the outcome of the disease. In ulcerative colitis, there are several therapies available, depending on the stage of the disease. Aminosalicylates, corticosteroids, and cyclosporine are used to treat mild, moderate, and severe disease, respectively. In Crohn’s disease, drug choices are dependent on both location and behavior of the disease. Nowadays, advances in treatments for IBD have included biological therapies, based mainly on monoclonal antibodies or fusion proteins, such as anti-TNF drugs. Notwithstanding the high cost involved, these biological therapies show a high index of remission, enabling a significant reduction in cases of surgery and hospitalization. Furthermore, migration inhibitors and new cytokine blockers are also a promising alternative for treating patients with IBD. In this review, an analysis of literature data on biological treatments for IBD is approached, with the main focus on therapies based on emerging recombinant biomolecules.

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