Disease Colitis Research Articles

Navigating the complexities of drug development for inflammatory bowel disease.

Inflammatory bowel disease (IBD) - consisting of ulcerative colitis and Crohn's disease - is a complex, heterogeneous, immune-mediated inflammatory condition with a multifactorial aetiopathogenesis. Despite therapeutic advances in this arena, a ceiling effect has been reached with both single-agent monoclonal antibodies and advanced small molecules. Therefore, there is a need to identify novel targets, and the development of companion biomarkers to select responders is vital. In this Perspective, we examine how advances in machine learning and tissue engineering could be used at the preclinical stage where attrition rates are high. For novel agents reaching clinical trials, we explore factors decelerating progression, particularly the decline in IBD trial recruitment, and assess how innovative approaches such as reconfiguring trial designs, harmonizing end points and incorporating digital technologies into clinical trials can address this. Harnessing opportunities at each stage of the drug development process may allow for incremental gains towards more effective therapies.

Association between 23 drugs and inflammatory bowel disease: a two-sample Mendelian randomization study.

Inflammatory bowel disease (IBD) is a group of diseases characterized by chronic and recurrent inflammation of the gastrointestinal tract. The etiology of IBD remains multifaceted and poorly understood, resulting in limited treatment options that primarily target disease induction and remission maintenance. Thus, the exploration of novel therapeutic options for IBD among existing medications is advantageous. Mendelian randomization analysis (MR) serves as a valuable tool in investigating the relationship between drugs and diseases. In this study, MR analysis was employed to investigate the potential causal relationship between 23 approved drugs for the treatment of various diseases and IBD. We performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) statistics. The inverse variance weighting (IVW) method was used as the main analysis method, supplemented by the remaining four methods (weighted median, MR Egger regression, simple and weighted models), and Meta-analysis was performed to expand the sample size to obtain a more reliable composite causal effect. Finally, Cochran's Q statistic and the MR-Egger test for directed pleiotropy were applied to determine whether significant heterogeneity or directed pleiotropy existed. In the main MR analysis (IVW), drugs with a negative causal association with the risk of IBD were immunosuppressant {OR (95% CI) = 0.7389 [0.6311-0.8651], p = 0.0046} and diabetes drugs {OR (95% CI) = 0.9266 [0.8876-0.9674], p = 0.0058}. A positive causal association with the risk of IBD was found for salicylic acid and derivatives {OR (95% CI) = 1.2737 [1.0778-1.5053], p = 0.0345}. Negative causal associations with UC risk were identified for immunosuppressants {OR (95% CI) = 0.6660 [0.5133-0.8640], p = 0.0169} and diabetes medications {OR (95% CI) = 0.9020 [0.8508-0.9551], p = 0.0046}; positive causal associations with UC risk were found for β-receptor blockers {OR (95% CI) = 1.1893 [1.0823-1.3070], p = 0.0046}. A negative causal association with the risk of CD was found for immunosuppressants {OR (95% CI) = 0.6957 [0.5803-0.8341], p = 0.0023}. There was no statistically significant association between the remaining 19 drugs and IBD and subtypes. This MR study provides evidence suggesting that immunosuppressants have a mitigating effect on the risk of IBD and demonstrate consistent efficacy in subtypes of ulcerative colitis (UC) and Crohn's disease (CD). Additionally, diabetes medications show potential in reducing the risk of IBD, particularly in cases of UC, while β-blockers may elevate the risk of UC. Conversely, salicylic acid and its derivatives may increase the risk of IBD, although this effect is not consistently observed in the subtypes of the disease. These findings offer new insights into the prevention and management of IBD.

Faecalibacterium prausnitzii A2-165 metabolizes host- and media-derived chemicals and induces transcriptional changes in colonic epithelium in GuMI human gut microphysiological system.

Aim: Recently, a GuMI gut microphysiological system has been established to coculture oxygen-intolerant Faecalibacterium prausnitzii (F. prausnitzii) A2-165 with organoids-derived primary human colonic epithelium. This study aims to test if this GuMI system applies to different donors with different healthy states and uses metabolomics to reveal the role of gut microbes in modulating host- and diet-derived molecules in the gut lumen. Methods: Organoids-derived colonic monolayers were generated from an uninflamed region of diverticulitis, ulcerative colitis, and Crohn's disease patients and then integrated into the GuMI system to coculture with F. prausnitzii A2-165 for 2 to 4 days. Apical media was collected for metabolomic analysis. Targeted metabolomics was performed to profile 169 polar chemicals under three conditions: conventional static culture without bacteria, GuMI without bacteria, and GuMI with F. prausnitzii. The barrier function of monolayers was measured using transepithelial resistance. Results: GuMI successfully cocultured patient-derived monolayers and F. prausnitzii for up to 4 days, with active bacterial growth. Introducing flow and oxygen gradient significantly increases the barrier function, while exposure to F. prausnitzii slightly increases the barrier function. Targeted metabolomics screened 169 compounds and detected 76 metabolites, of which 70 significantly differed between at least two conditions. F. prausnitzii significantly modulates the levels of nucleosides, nucleobases, and amino acids on the apical side. Further analysis suggests that F. prausnitzii changes the mRNA level of 260 transcription factor genes in colonic epithelial cells. Conclusion: The GuMI physiomimetic system can maintain the coculture of F. prausnitzii and colonic epithelium from different donors. Together with metabolomics, we identified the modulation of F. prausnitzii in extracellular chemicals and colonic epithelial cell transcription in coculture with human colonic epithelium, which may reflect its function in gut lumen in vivo.

Alleviating depressive-like behavior in DSS-induced colitis mice: Exploring naringin and poncirin from Poncirus trifoliata extracts

Patients with inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), often have concomitant mental disorders such as depression and anxiety. Therefore, a bidirectional approach involving the gut and brain axes is necessary for the prevention and treatment thereof. In this study, we explored the potential of Poncirus trifoliata extract (PT), traditionally known for its neuroprotective effects against gastrointestinal diseases, as a natural treatment agent for IBD in a dextran sulfate sodium (DSS)-induced colitis model. Oral administration of PT ameliorated weight loss and inflammatory responses in mice with DSS-induced colitis. Furthermore, PT treatment effectively restored the colon length and ameliorated enterocyte death by inhibiting DSS-induced reactive oxygen species (ROS)-mediated necroptosis. The main bioactive components of PT, poncirin and naringin, confirmed using ultra-performance liquid chromatography-quadrupole time-of-flight (UPLC-qTOF), can be utilized to regulate necroptosis. The antidepressant-like effects of PT were confirmed using open field test (OFT) and tail suspension test (TST). PT treatment also restored vascular endothelial cell integrity in the hippocampus. In the Cornu Ammonis 1 (CA1) and dentate gyrus (DG) regions of the hippocampus, PT controlled the neuroinflammatory responses of proliferated microglia. In conclusion, PT, which contains high levels of poncirin and naringin, has potential as a bidirectional therapeutic agent that can simultaneously improve IBD-associated intestinal and mental disorders.

Current Developments in the Prevention and Improvement of Intestinal Disorders: A Mini-Review.

Recently, the number of patients who manifest intestinal disorders has increased. Particularly, Irritable Bowel Syndrome (IBS) patients and Inflammatory Bowel Disease (IBD) patients, which include Ulcerative Colitis (UC) and Crohn's Disease (CD), are on the rise, especially in the young generation. Behcet's disease (an autoimmune disease) and bowel obstruction are also common intestinal disorders. Furthermore, colorectal cancer, including colon and rectum cancer and small intestinal cancer, are the typical disorders in the intestine. Other disorders in the digestive tract are infectious diseases like Helicobacter pylori infection. Even though symptomatic treatments have been increasing for the treatment of intestinal disorders, the ways of improving and preventing these diseases are still controversial. The progress of medicine and treatment is rapid. However, recent approaches to the prevention and improvement of these intestinal disorders are suppressing dysbiosis and preventing chronic inflammation. This mini-review discusses the hypothesis of whether the improvement of the diet is a preferable choice for the prevention of these intestinal disorders. Dietary interventions are beneficial for the prevention and improvement of intestinal disorders since the first approach to intestinal disorders is dietary intervention. The Mediterranean diet, the diet from the 5-a-day campaign, and the Japanese diet are well-known healthy dietary strategies. A healthy diet regimen is not only beneficial for the prevention of intestinal disorders but also a useful strategy to reduce stress and ameliorate mental illness. In addition, the intake of phytochemicals is good for keeping healthy gut microbiota and preventing intestinal disorders. Furthermore, vitamin D3 intake with these phytochemicals works as an adjuvant to improve gut microbiota and upregulate immune responses. As a result, the decreasing production of TNF-α ameliorates chronic inflammation and intestinal disorders at an early stage. In recent years, prevention of the non-disease condition "ME-BYO" has been a popular approach for healthy and long living in Japan. This idea prevents the manifestation of diseases before the onset and is also applicable to intestinal disorders. This mini-review discusses ways of preventing and ameliorating intestinal disorders.

Molecular modeling and simulation approaches to characterize potential molecular targets for burdock inulin to instigate protection against autoimmune diseases.

In the current study, we utilized molecular modeling and simulation approaches to define putative potential molecular targets for Burdock Inulin, including inflammatory proteins such as iNOS, COX-2, TNF-alpha, IL-6, and IL-1β. Molecular docking results revealed potential interactions and good binding affinity for these targets; however, IL-1β, COX-2, and iNOS were identified as the best targets for Inulin. Molecular simulation-based stability assessment demonstrated that inulin could primarily target iNOS and may also supplementarily target COX-2 and IL-1β during DSS-induced colitis to reduce the role of these inflammatory mechanisms. Furthermore, residual flexibility, hydrogen bonding, and structural packing were reported with uniform trajectories, showing no significant perturbation throughout the simulation. The protein motions within the simulation trajectories were clustered using principal component analysis (PCA). The IL-1β-Inulin complex, approximately 70% of the total motion was attributed to the first three eigenvectors, while the remaining motion was contributed by the remaining eigenvectors. In contrast, for the COX2-Inulin complex, 75% of the total motion was attributed to the eigenvectors. Furthermore, in the iNOS-Inulin complex, the first three eigenvectors contributed to 60% of the total motion. Furthermore, the iNOS-Inulin complex contributed 60% to the total motion through the first three eigenvectors. To explore thermodynamically favorable changes upon mutation, motion mode analysis was carried out. The Free Energy Landscape (FEL) results demonstrated that the IL-1β-Inulin achieved a single conformation with the lowest energy, while COX2-Inulin and iNOS-Inulin exhibited two lowest-energy conformations each. IL-1β-Inulin and COX2-Inulin displayed total binding free energies of - 27.76kcal/mol and - 37.78kcal/mol, respectively, while iNOS-Inulin demonstrated the best binding free energy results at - 45.89kcal/mol. This indicates a stronger pharmacological potential of iNOS than the other two complexes. Thus, further experiments are needed to use inulin to target iNOS and reduce DSS-induced colitis and other autoimmune diseases.

Acute Kidney Injury in Inflammatory Bowel Disease Patients: A Nationwide Comparative Analysis

Rationale & ObjectiveAbout 25-40% of patients with inflammatory bowel diseases (IBD) may have extra-intestinal manifestations, mainly involving the liver, skin, and joints. Kidney involvement in patients with IBD has been reported, but there are no estimates of its prevalence in population-based studies in the US. We compared the frequency of AKI among hospitalizations with IBD to hospitalizations with collagen vascular diseases and hospitalizations without IBD or collagen vascular diseases. Study DesignRetrospective, population-based cohort study Setting and ParticipantsHealthcare Cost and Utilization Project (HCUP)--Nationwide Inpatient Sample (NIS) database. ExposureTK OutcomesAcute kidney injury (AKI) and AKI requiring dialysis. Analytical ApproachRegression models were used to compare occurrence of AKI among groups. Inverse probability of treatment weighting (IPTW) applied to balance groups on covariates. ResultsThe final sample comprised of 5,735,804 hospitalizations, including 57,121 with IBD, 159,930 with collagen vascular diseases and 5,518,753 without IBD or collagen vascular diseases. AKI was observed in 13%, 15%, and 12.2% of hospitalizations with IBD, collagen vascular diseases, and the general population, respectively. When adjusting for demographic, hospital, and clinical characteristics using IPTW, hospitalizations with IBD had higher odds of being diagnosed with AKI compared to both the collagen vascular diseases (OR, 1.32; 95% CI, 1.27-1.38) and general population (OR 1.27, 95% CI, 1.23-1.31), and also had higher odds of being diagnosed with AKI requiring dialysis compared to collagen vascular diseases (OR, 1.59; 95% CI 1.31, 1.94) and general population (OR,1.45; 95% CI 1.25, 1.68). LimitationsCross-sectional analysis, underreporting of ICD codes, and analyses relevant to in-hospital stays only. ConclusionsThe prevalence and risk of AKI among hospitalization with IBD is greater than that of the hospitalization in the collagen vascular diseases and the general population cohort. Coexisting kidney disease should be considered among patients with a known diagnosis of IBD.

Granzyme B PET Imaging for Assessment of Disease Activity in Inflammatory Bowel Disease.

Developing a noninvasive imaging method to detect immune system activation with a high temporal resolution is key to improving inflammatory bowel disease (IBD) management. In this study, granzyme B (GZMB), typically released from cytotoxic T and natural killer cells, was targeted using PET with 68Ga-NOTA-GZP (where GZP is β-Ala-Gly-Gly-Ile-Glu-Phe-Asp-CHO) to detect early intestinal inflammation in murine models of colitis. Methods: Bioinformatic analysis was used to assess the potential of GZMB as a biomarker for detecting IBD and predicting response to treatment. Human active and quiescent Crohn disease and ulcerative colitis tissues were stained for GZMB. We used IL-10-/- mice treated with dextran sulfate sodium (DSS) as an IBD model, wild-type C57BL/6J mice as a control, and anti-tumor necrosis factor as therapy. We used a murine GZMB-binding peptide conjugated to a NOTA chelator (NOTA-GZP) labeled with 68Ga as the PET tracer. PET imaging was conducted at 1, 3, and 4 wk after colitis induction to evaluate temporal changes. Results: Bioinformatic analysis showed that GZMB gene expression is significantly upregulated in human ulcerative colitis and Crohn disease compared with the noninflamed bowel by 2.98-fold and 1.92-fold, respectively; its expression is lower by 2.16-fold in treatment responders than in nonresponders. Immunofluorescence staining of human tissues demonstrated a significantly higher GZMB in patients with active than with quiescent IBD (P = 0.032).68Ga-NOTA-GZP PET imaging showed significantly increased bowel uptake in IL-10-/- mice with DSS-induced colitis compared with vehicle-treated IL-10-/- mice (SUVmean, 0.75 vs. 0.24; P < 0.001) and both vehicle- and DSS-treated wild-type mice (SUVmean, 0.26 and 0.37; P < 0.001). In the IL-10-/- DSS-induced colitis model, the bowel PET probe uptake decreased in response to treatment with tumor necrosis factor-α (SUVmean, 0.32; P < 0.001). There was a 4-fold increase in colonic uptake of 68Ga-NOTA-GZP in the colitis model compared with the control 1 wk after colitis induction. The uptake gradually decreased to approximately 2-fold by 4 wk after IBD induction; however, the inflamed bowel uptake remained significantly higher than control at all time points (week 4 SUVmean, 0.23 vs. 0.08; P = 0.001). Conclusion: GZMB is a promising biomarker to detect active IBD and predict response to treatment. This study provides compelling evidence to translate GZMB PET for imaging IBD activity in clinical settings.

Conception, pregnancy and inflammatory bowel disease-Current concepts for the practising clinician.

The peak incidence of inflammatory bowel disease (IBD) coincides with a woman's prime reproductive years. The management of IBD during pregnancy can be challenging for healthcare professionals, underpinning the need for a multi-disciplinary approach with shared decision-making with the patient. Pre-conception counselling can address patient concerns, improve pregnancy specific IBD patient knowledge and provide a personalized risk assessment, to ensure optimal maternal and fetal outcomes. Most women with IBD have fertility rates comparable with the general population, although voluntary childlessness is common among women with IBD. IBD disease activity at conception and during pregnancy is a key determinant of the course of IBD during pregnancy. Active IBD during pregnancy is associated with adverse pregnancy-related outcomes, including spontaneous abortion, small for gestational age baby and preterm birth, emphasizing the importance of ensuring disease remission prior to conception. Most IBD medications (5-aminosalicylates, thiopurines if already initiated pre-conception, corticosteroids and biologic medications) are considered safe and low risk during pregnancy and breastfeeding, except for methotrexate, JAK-inhibitors, ozanimod and allopurinol and maintaining remission throughout gestation should be the priority. Most women with IBD can have a vaginal delivery, but cesarean section should be considered in active perianal disease and history of ileal pouch surgery. This narrative review outlines the current evidence for themanagement of IBD in pregnancy, as well as considering the pre-conceptual and post-partum period.

Role of Neutrophil Lymphocyte Ratio in Prediction of Disease Activity in Ulcerative Colitis Disease

Role of Neutrophil Lymphocyte Ratio in Prediction of Disease Activity in Ulcerative Colitis Disease

A prediction of the CRNDE role by modulating NF-κB pathway in inflammatory bowel disease (IBD)

Long non-coding RNAs (lncRNAs) regulate multiple pathways and cellular mechanisms. Recent research has emphasized their involvement in the pathogenesis of complex diseases, such as Inflammatory Bowel Disease (IBD) which is characterized by chronic inflammation of the intestines. The two most common types of IBD are ulcerative colitis and Crohn's disease. CRNDE lncRNA was initially detected in colorectal cancer (CRC) and found to be involved in the tumorigenesis pathways. Further studies revealed the role of CRNDE in activating inflammation and promoting the release of inflammatory cytokines. This study utilizes the RNA-seq data analysis and bioinformatics tools to clarify the role of CRNDE in the IBD pathogenesis and confirms its expression in inflamed HT-29 and Caco-2 cell lines and also colonic and blood samples of UC patients and controls ex vivo. Based on our results, CRNDE was significantly upregulated in IBD samples compared to controls in RNA-seq data analysis and Real-time PCR of inflamed HT-29 cell line and colonic biopsies from UC patients. Additionally, predicted that its expression is positively correlated with the pro-inflammatory cytokines production. CRNDE interactions was investigated with several inflammation-related miRNAs and regulatory proteins computationally. Thus, CRNDE upregulation in the colon of IBD patients could be involved in IBD pathogenesis by promoting inflammatory pathways and targeting anti-inflammatory miRNAs.

The Role of Wheatgrass in Colorectal Cancer: A Review of the Current Evidence.

The etiology of colon cancer is either genetic in nature or results from inflammatory bowel diseases such as ulcerative colitis and Crohn's disease; nevertheless, dietary habits play a crucial role in the disease. Wheatgrass is a dietary supplement that is rich in vitamins, minerals, and antioxidants which contribute to health promotion in cardiovascular diseases, liver disease, blood diseases, diabetes, and inflammatory bowel diseases, as well as in several types of cancers, such as oral squamous cell cancer, cervical cancer, and breast cancer. In colorectal cancer (CRC), the prospect that wheatgrass possesses anti-inflammatory, antioxidant, and anticancer properties, and its use as an adjunctive therapy, have been minimally investigated and evidence is still limited. In this review, we compiled the available evidence pertaining to wheatgrass and its likely impact on CRC, described the pathways of inflammation in which wheatgrass could possibly play a role, and identified future research needs on the subject.

Exploring the association between microscopic colitis and celiac disease: A comprehensive analysis using the national in-patient data (2016-2019).

Several investigations suggested correlation between microscopic colitis (MC) and celiac disease (CD). This study aimed to examine this relationship using large-sized, population-based data with adequate control for confounding factors. This study employed the National Inpatient Sample (NIS) database over 4 years (2016-2019). Patients with/without MC in the presence/absence of CD were identified through ICD-10 codes. Univariate and multi-variate analyses involving odds ratios (OR) and 95% confidence intervals (CI) were performed. Overall, 26,836,118 patients were analyzed. Of whom, 6,836 patients had MC (n = 179 with CD and n = 6,657 without CD). The mean hospital stay was not significantly different between both groups (5.42 ± 5.44 days vs. 4.95 ± 4.66 days, P = 0.202). The univariate analysis revealed a significant association between MC and CD (OR = 22.69, 95% [19.55, 26.33], P < 0.0001). In the multi-variate analysis, which adjusted for potential confounders including age, race, hospital region, hospital teaching status, ZIP income, smoking status, alcohol overuse, hypertension, diabetes mellitus, lipidemia-related disorders, non-steroidal anti-inflammatory drug use, and selected auto-immune diseases, the association remained significant (OR = 15.71, 95% CI [13.52, 18.25], P < 0.0001). Moreover, in patients with MC, the presence of CD emerged as a significant, independent variable of in-hospital mortality in univariate (OR = 2.87, 95% [1.14, 7.21], P = 0.025) and multi-variate (OR = 3.37, 95% CI [1.32, 8.60], P = 0.011) analyses. This study establishes a probable link between MC and CD, backed by both univariate and multi-variate analyses, while also identifying CD as an independent risk factor for increased mortality among MC patients. These findings need to be validated in real-world clinical studies.

Differentiation Between Ulcerative Colitis and Crohn's Disease Using Abdominal Computed Tomography in Patients With First-Time Inflammatory Bowel Disease.

Background Ulcerative colitis (UC) and Crohn's disease (CD) are classified as inflammatory bowel diseases (IBDs). However, they have different pathogeneses and treatment strategies and need to be differentiated. Purpose To determine the feasibility of differentiating UC from CD in patients with first-time IBD based on simple abdominal computed tomography (CT) findings. Methods We conducted a retrospective study of patients diagnosed with IBD for the first time at our hospital between January and December 2021. Age, sex, white blood cell count, albumin concentration, C-reactive protein concentration, visceral fat area, subcutaneous fat area, and psoas major volume were extracted and used to differentiate the two groups. Results Forty-three patients were selected. Their mean age was 35.60 ± 17.19 years, and 32 were male, while 11 were female. The visceral fat cross-sectional area was 51.80 cm2 for UC and 21.10 cm2 for CD (p < 0.01). The subcutaneous fat cross-sectional area was 108.30 cm2 for UC and 66.30 cm2 for CD (p = 0.049). The total protein concentration was 6.15 g/L for UC and 6.60 g/L for CD (p = 0.012). Receiver operating characteristic curve analysis of the visceral and subcutaneous fat cross-sectional areas showed areas under the curve, 95% confidence intervals, sensitivities, and specificities of 0.750 and 0.675, 0.603-0.897 and 0.507-0.844, 0.810 and 1.00, and 0.591 and 0.409, respectively, at cutoffs of 26.53 and 36.6 cm2. Conclusions The visceral and subcutaneous fat cross-sectional areas determined with simple abdominal CT can differentiate UC from CD in patients with first-time IBD.

Management of inflammatory bowel disease in the emergency setting: the MIBODI international survey and evidence-based practices.

This study aimed to evaluate the impact of the WSES-AAST guidelines in clinical practice and to investigate the knowledge, attitudes, and practices of emergency surgeons in managing the complications of ulcerative colitis (UC) and Crohn's disease (CD). The MIBODI survey is a cross-sectional study among WSES members designed as an international web-based survey, according to the Checklist for Reporting Results of Internet E-Surveys, to collect data on emergency surgeons' knowledge, attitudes, and practices concerning the management of patients presenting with acute complications of CD and UC. The questionnaire was composed of 30 questions divided into five sections: (1) demographic data, (2) primary evaluation, (3) non-operative management, (4) operative management, and (5) perianal sepsis management. Two hundred and forty-two surgeons from 48 countries agreed to participate in the survey. The response rate was 24.2% (242/1000 members on WSES mail list). Emergency surgeons showed high adherence to recommendations for 6 of the 21 assessed items, with a "correct" response rate greater than or equal to 60%, according to WSES-AAST recommendations. Nine critical issues were highlighted, with correct answers at a rate of less than 50%. Inflammatory bowel disease is a complex disease that requires a multidisciplinary approach with close collaboration between gastroenterologists and surgeons. Emergency surgeons play a crucial role in managing complications related to IBD. One year after publication, the MIBODI study showed significant global implementation of the WSES-AAST guidelines in clinical practice, offering an imperative tool in the improved management of IBD in emergency and urgent settings.

Amelioration of Dextran Sodium Sulfate-Induced Colitis in Mice through Oral Administration of Palmitoylethanolamide.

Inflammatory bowel disease (IBD) is a group of chronic disorders characterized by pain, ulceration, and the inflammation of the gastrointestinal tract (GIT) and categorized into two major subtypes: ulcerative colitis (UC) and Crohn's disease. The inflammation in UC is typically restricted to the mucosal surface, beginning in the rectum and extending through the entire colon. UC patients typically show increased levels of pro-inflammatory cytokines, leading to intestinal epithelial apoptosis and mucosal inflammation, which impair barrier integrity. Chronic inflammation is associated with the rapid recruitment and inappropriate retention of leukocytes at the site of inflammation, further amplifying the inflammation. While UC can be managed using a number of treatments, these drugs are expensive and cause unwanted side effects. Therefore, a safe and effective treatment for UC patients is needed. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide and an analog of the endocannabinoid anandamine. PEA administration has been found to normalize intestinal GIT motility and reduce injury in rodents and humans. In the current study, we examined the efficacy of PEA encapsulated in phytosomes following oral administration in experimental ulcerative colitis. Here, we showed that PEA at a human-equivalent dose of 123 mg/kg (OD or BID) attenuated DSS-induced experimental colitis as represented by the reduction in clinical signs of colitis, reduction in gross mucosal injury, and suppression of leukocyte recruitment at inflamed venules. These findings add to the growing body of data demonstrating the beneficial effects of PEA to control the acute phase of intestinal inflammation occurring during UC.

A systematic review and meta-analysis of extra-intestinal manifestation of inflammatory bowel disease in the Eastern Mediterranean Region (EMRO) countries.

Inflammatory bowel disease which is subgrouped mainly to ulcerative colitis and Crohn's disease is thought to be a multi-organ disease. Most organs can be involved in the disease course in addition to gastrointestinal tract involvement. In this systematic review we aimed to assess the prevalence of these manifestations in Eastern Mediterranean Regional Office (EMRO) countries. The present systematic review and meta-analysis study was performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. Joanna Briggs Institute (JBI) Critical Appraisal Checklist was admired for the quality evaluation of the included studies. For determining the heterogeneity, we used Cochran test and I2 statistics. Finally, 12 studies were included in our study. Based on the results of our study the prevalence of arthritis in ulcerative colitis and Crohn's disease patients was 7.1% (95% CI: 2.6-18.2%) and 13.5% (95% CI: 2.6-47.3%), respectively. Prevalence of arthralgia in ulcerative colitis patients was 18.4% (95% CI: 14.3-23.3%). skin involvement prevalence was 9.9% (95% CI 4.7-19.6%) in inflammatory bowel disease (IBD) patients. ocular involvement prevalence was 7.2% (95% CI 17-25.8%) in IBD patients. PSC prevalence in ulcerative colitis and Crohn's disease patients was 3.5% (95% CI: 1.7-7.3%) and 2.7% (95% CI: 1.3-5.5%), respectively. Based on the results of this study arthralgia and arthritis were the most common extra-intestinal manifestation of IBD followed by dermatologic and ocular involvements. This extra-intestinal manifestation can challenge the patients' management and identifying their pattern is important during the disease course.

Inflammatory bowel disease and allergic diseases: A Mendelian randomization study.

Inflammatory bowel disease (IBD) and allergic diseases possess similar genetic backgrounds and pathogenesis. Observational studies have shown a correlation, but the exact direction of cause and effect remains unclear. The aim of this Mendelian randomization (MR) study is to assess bidirectional causality between inflammatory bowel disease and allergic diseases. We comprehensively analyzed the causal relationship between inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) and allergic disease (asthma, Hay fever, and eczema) as a whole, allergic conjunctivitis (AC), atopic dermatitis (AD), allergic asthma (AAS), and allergic rhinitis (AR) by performing a bidirectional Mendelian randomization study using summary-level data from genome-wide association studies. The analysis results mainly came from the random-effects model of inverse variance weighted (IVW-RE). In addition, multivariate Mendelian randomization (MVMR) analysis was conducted to adjust the effect of body mass index (BMI) on the instrumental variables. The IVW-RE method revealed that IBD genetically increased the risk of allergic disease as a whole (OR = 1.03, 95% CI = 1.01-1.04, fdr.p = .015), AC (OR = 1.04, 95% CI = 1.01-1.06, fdr.p = .011), and AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = .004). Subgroup analysis further confirmed that CD increased the risk of allergic disease as a whole (OR = 1.02, 95% CI = 1.00-1.03, fdr.p = .031), AC (OR = 1.03, 95% CI = 1.01-1.05, fdr.p = .012), AD (OR = 1.06, 95% CI = 1.02-1.09, fdr.p = 2E-05), AAS (OR = 1.05, 95% CI = 1.02-1.08, fdr.p = .002) and AR (OR = 1.03, 95% CI = 1.00-1.07, fdr.p = .025), UC increased the risk of AAS (OR = 1.02, 95% CI = 0.98-1.07, fdr.p = .038). MVMR results showed that after taking BMI as secondary exposure, the causal effects of IBD on AC, IBD on AD, CD on allergic disease as a whole, CD on AC, CD on AD, CD on AAS, and CD on AR were still statistically significant. No significant association was observed in the reverse MR analysis. This Mendelian randomized study demonstrated that IBD is a risk factor for allergic diseases, which is largely attributed to its subtype CD increasing the risk of AC, AD, ASS, and AR. Further investigations are needed to explore the causal relationship between allergic diseases and IBD.

Evaluación de la calidad de vida de los pacientes con enfermedad inflamatoria intestinal

IntroductionUlcerative colitis (UC) and Crohn's disease (CD) are diseases that cause a significant impact on patients’ quality of life.The aim of this study is to assess the impact of inflammatory bowel disease (IBD) on health-related quality of life (HRQoL). Material and methodsObservational, descriptive, cross-sectional study, carried out at Torrecárdenas Hospital (Almería). Patients over 14 years of age diagnosed with CD or UC were included.For the assessment of HRQoL, the reduced 9-item IBDQ-9 questionnaire was used. Results106 patients with a mean age of 44 years were included, with a female predominance. Forty-five percent of the patients in the sample had UC compared to 55% with CD. Of the patients, 69.8% were in clinical remission.The median questionnaire score was 60.8 points out of 100.Statistically significant differences were observed between sexes, with worse HRQoL for females. No differences were observed between patients with UC and CD. Differences were also detected between patients who underwent surgery and those who did not.A negative association was observed between the number of flares and the questionnaire score. ConclusionsIn our study population, there is an acceptable HRQoL, with no differences observed between CD and UC.Female sex, absence of clinical remission, number of previous outbreaks, and surgery have a negative association with HRQoL.

Study on the Protective Effect and Mechanism of Umbilicaria esculenta Polysaccharide in DSS-Induced Mice Colitis and Secondary Liver Injury.

This study aimed to explore the ameliorative effects and potential mechanisms of Huangshan Umbilicaria esculenta polysaccharide (UEP) in dextran sulfate sodium-induced acute ulcerative colitis (UC) and UC secondary liver injury (SLI). Results showed that UEP could ameliorate both colon and liver pathologic injuries, upregulate mouse intestinal tight junction proteins (TJs) and MUC2 expression, and reduce LPS exposure, thereby attenuating the effects of the gut-liver axis. Importantly, UEP significantly downregulated the secretion levels of TNF-α, IL-1β, and IL-6 through inhibition of the NF-κB pathway and activated the Nrf2 signaling pathway to increase the expression levels of SOD and GSH-Px. In vitro, UEP inhibited the LPS-induced phosphorylation of NF-κB P65 and promoted nuclear translocation of Nrf2 in RAW264.7 cells. These results revealed that UEP ameliorated UC and SLI through NF-κB and Nrf2-mediated inflammation and oxidative stress. The study first investigated the anticolitis effect of UEP, suggesting its potential for the treatment of colitis and colitis-associated liver disease.