Inflammatory Potential of the Diet and Incidence of Crohn’s Disease and Ulcerative Colitis in the EPIC-Spain Cohort

Diet may influence the development of inflammatory bowel disease through the modulation of inflammation. We investigated whether the inflammatory potential of the diet is associated with the risk of Crohn’s disease (CD) and ulcerative colitis (UC) in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The study included 32,633 participants aged 29–69 years. The inflammatory potential of the diet was measured by using an inflammatory score of the diet (ISD) based on a baseline dietary history questionnaire. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 21 years (674,547 person-years) of follow-up, 32 and 57 participants developed CD and UC, respectively. In multivariable analysis, a one-standard deviation (SD) increment in the ISD (two-unit increase) was associated with a higher risk of CD (HR of 1.71; 95% CI: 1.05–2.80; p = 0.031). By contrast, ISD was not associated with UC (HR for one-SD increment of 0.89; 95% CI: 0.66–1.19; p = 0.436). Our results suggest that consuming a more pro-inflammatory diet may contribute to the risk of CD, supporting that a healthy diet might be beneficial in its prevention. Further, larger studies are needed to verify these findings.

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Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study

BMJ ◽

10.1136/bmj.n1554 ◽

2021 ◽

pp. n1554

Author(s):

Neeraj Narula ◽

Emily C L Wong ◽

Mahshid Dehghan ◽

Andrew Mente ◽

Sumathy Rangarajan ◽

...

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Cohort Study ◽

Crohn’S Disease ◽

Food Intake ◽

Crohn's Disease ◽

Processed Food ◽

Hazard Ratios ◽

Inflammatory Bowel

Abstract Objective To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD). Design Prospective cohort study. Setting 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). Participants 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. Main outcome measures The main outcome was development of IBD, including Crohn’s disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. Results Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn’s disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn’s disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD. Conclusions Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods. Study registration ClinicalTrials.gov NCT03225586 .

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Occurrence of Colorectal Cancer and the Influence of Medical Treatment in Patients With Inflammatory Bowel Disease: A Danish Nationwide Cohort Study, 1997 to 2015

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa340 ◽

2021 ◽

Author(s):

Petra Weimers ◽

Dorit Vedel Ankersen ◽

Ellen Christine Leth Løkkegaard ◽

Johan Burisch ◽

Pia Munkholm

Keyword(s):

Colorectal Cancer ◽

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Medical Treatment ◽

Bowel Disease ◽

Cox Regression ◽

Biologic Treatment ◽

Inflammatory Bowel

Abstract Background The risk of colorectal cancer (CRC) for patients with inflammatory bowel disease (IBD) has previously been investigated with conflicting results. We aimed to investigate the incidence and risk of CRC in IBD, focusing on its modification by treatment. Methods All patients with incident IBD (n = 35,908) recorded in the Danish National Patient Register between 1997 and 2015 (ulcerative colitis: n = 24,102; Crohn’s disease: n = 9739; IBD unclassified: n = 2067) were matched to approximately 50 reference individuals (n = 1,688,877). CRC occurring after the index date was captured from the Danish Cancer Registry. Exposure to medical treatment was divided into categories including none, systemic 5-aminosalicylates, immunomodulators, and biologic treatment. The association between IBD and subsequent CRC was investigated by Cox regression and Kaplan-Meier estimates. Results Of the IBD patients, 330 were diagnosed with CRC, resulting in a hazard ratio (HR) of 1.15 (95% confidence interval [CI], 1.03-1.28) as compared with the reference individuals. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the HR decreased to 0.80 (95% CI, 0.71-0.92). Patients with ulcerative colitis receiving any medical treatment were at significantly higher risk of developing CRC than patients with ulcerative colitis who were not given medical treatment (HR, 1.35; 95% CI, 1.01-1.81), whereas a similar effect of medical treatment was not observed in patients with Crohn’s disease or IBD unclassified. Conclusions Medical treatment does not appear to affect the risk of CRC in patients with IBD. The overall risk of developing CRC is significantly increased in patients with IBD as compared with the general population. However, when excluding patients diagnosed with CRC within 6 months of their IBD diagnosis, the elevated risk disappears.

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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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PATIENTS WITH INFLAMMATORY BOWEL DISEASE PERSPECTIVE ON COVID-19 AND HEALTH CARE SERVICE DURING THE PANDEMIC

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.120 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S50-S51

Author(s):

Randi Opheim ◽

Kristian Moum ◽

Bjørn Moum

Keyword(s):

Ulcerative Colitis ◽

Health Care ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Medical Treatment ◽

Biological Therapy ◽

Care Service ◽

Health Care Service ◽

Inflammatory Bowel

Abstract Background Patients with inflammatory bowel diseases (IBD) have experienced changes to the routine management of their conditions during the coronavirus disease (COVID-19) pandemic. The disease as well IBD treatment frequently require immunosuppressant medications, which could increase their risk of infection. The aim of this study was to determine patients’ experience of the health care service, including the restrictions of hospitals visits made in Norway from Mars 12th 2020. Method From June 18 to September 18 2020, all patients at the IBD outpatient clinic at Oslo University Hospital in Norway on biological therapy or other immunosuppressant’s were included. A questionnaire including patients concerns regarding their disease, medical therapy and COVID-19, as well as their health care service needs in follow-up during the COVID-19 pandemic. Results Altogether 506 IBD patients answered a paper-based questionnaire. The mean age was 40.78 (SD 14.71), 289/506 (57%) men, ulcerative colitis 199/506 (39%), Crohn’s disease 307/506 (61%). Sixty-three patients (12.5%) used biological therapy in combination with azathioprine or steroids. Ninety-one (18.2%) were in obligated quarantine with negative test. Five patients (4.9%) tested positive to SARS- CoV-2 of the 98 patients tested, (1.0% of the total sample). One third of the IBD patients perceived they had increased risk for being infected by SARS- CoV-2 because of the immunosuppressive drugs they used. Nonetheless, 496/506 (98.6%) of the patients adhered to continuing their medication. One-hundred and sixty-one (32.3%) voluntarily isolated, and 21/506 (4.2%) was in sick leave being afraid of being infected. Furthermore, 20/506 (4.0%) cancelled their consultation because they were afraid of being infected from SARS- CoV-2 at the hospital. The hospital changed physical consultation to telephone consultation for 75/506 (15.0%) of the patients. Thirty-eight patients (7.6%) reported that they were afraid of going to the hospital because of restrictions due to the COVID-19 pandemic, and 18/506 (3.6%) did not feel safe when at hospital. Approximately half of the IBD patients (219/506) were satisfied with the information provided by physician about medical treatment for IBD and Covid-19 while 398/506 (77.3%) were satisfied with the information from health-care providers about restrictions due to COVID-19. There were no statistical differences between Crohn’s disease and ulcerative colitis. Conclusion IBD patients on biological treatment and immunosuppressives took precautions because of fear of being infected with SARS- CoV-2. At the same time, they adhere to medical treatment regimens and follow-up at the hospital. Most patients were satisfied with the information they received from physicians and other health-care workers. One percent tested positive to SARS-CoV-2.

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Physiological Basis for Novel Drug Therapies Used to Treat the Inflammatory Bowel Diseases I. Immunology and therapeutic potential of antiadhesion molecule therapy in inflammatory bowel disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00423.2004 ◽

2005 ◽

Vol 288 (2) ◽

pp. G169-G174 ◽

Cited By ~ 56

Author(s):

Gert Van Assche ◽

Paul Rutgeerts

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Adhesion Molecules ◽

Bowel Disease ◽

Intestinal Inflammation ◽

Therapeutic Potential ◽

Physiological Basis ◽

Inflammatory Bowel

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. They are also involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. In intestinal inflammation, many adhesion molecules are upregulated, but α4-integrins most likely hold a key position in directing leukocytes into the inflamed bowel wall. Therapeutic compounds directed against trafficking of leukocytes have been designed and are being developed as a novel class of drugs in the treatment of Crohn's disease and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Second, the changes in adhesion molecules and T cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered with respect to the therapeutic potential and the safety of antiadhesion molecule treatment. Antegren, or natalizumab, a humanized anti-α4 integrin IgG4 antibody, has been most extensively evaluated and may be close to registration. A more specific humanized α4β7-integrin MLN-02 has shown preliminary clinical efficacy in ulcerative colitis, and both antergren and MLN-02 appear to be very safe. Trials with the anti-ICAM-1 antisense oligonucleotide ISIS-2302 in steroid refractory Crohn's disease have provided conflicting efficacy data. In the near future, some of these novel biological agents may prove valuable therapeutic tools in the management of refractory inflammatory bowel disease, although it is too early to define the patient population that will benefit most from these agents.

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The Incidence of Deep Venous Thrombosis and Pulmonary Embolism among Patients with Inflammatory Bowel Disease: A Population-based Cohort Study

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615600 ◽

2001 ◽

Vol 85 (03) ◽

pp. 430-434 ◽

Cited By ~ 348

Author(s):

James Blanchard ◽

Donald Houston ◽

Andre Wajda ◽

Charles Bernstein

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Pulmonary Embolism ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Population Based ◽

Incidence Rates ◽

Increased Risk ◽

Inflammatory Bowel

Summary Background: There is an impression mostly from specialty clinics that patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolic disorders. Our aim was to determine the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) from a population-based database of IBD patients and, to compare the incidence rates to that of an age, gender and geographically matched population control group. Methods: IBD patients identified from the administrative claims data of the universal provincial insurance plan of Manitoba were matched 1:10 to randomly selected members of the general population without IBD by year, age, gender, and postal area of residence using Manitoba Health’s population registry. The incidence of hospitalization for DVT and PE was calculated from hospital discharge abstracts using ICD-9-CM codes 451.1, 453.x for DVT and 415.1x for PE. Rates were calculated based on person-years of follow-up for 1984-1997. Comparisons to the population cohort yielded age-adjusted incidence rate ratios (IRR). Rates were calculated based on person-years of follow-up (Crohn’s disease = 21,340, ulcerative colitis = 19,665) for 1984-1997. Results: In Crohn’s disease the incidence rate of DVT was 31.4/10,000 person-years and of PE was 10.3/10,000 person-years. In ulcerative colitis the incidence rates were 30.0/10,000 person-years for DVT and 19.8/10,000 person-years for PE. The IRR was 4.7 (95% CI, 3.5-6.3) for DVT and 2.9 (1.8-4.7) for PE in Crohn’s disease and 2.8 (2.1-3.7) for DVT and 3.6 (2.5-5.2) for PE, in ulcerative colitis. There were no gender differences for IRR. The highest rates of DVT and PE were seen among patients over 60 years old; however the highest IRR for these events were among patients less than 40 years. Conclusion: IBD patients have a threefold increased risk of developing DVT or PE.

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