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Crohn's disease (CD) is a complex and heterogeneous condition with no perfect preclinical model or cure. To address this, we explore adult stem cell-derived organoids that retain their tissue identity and disease-driving traits. We prospectively create a biobank of CD patient-derived organoid cultures (PDOs) from colonic biopsies of 53 subjects across all clinical subtypes and healthy subjects. Gene expression analyses enabled benchmarking of PDOs as tools for modeling the colonic epithelium in active disease and identified two major molecular subtypes: immune-deficient infectious CD (IDICD) and stress and senescence-induced fibrostenotic CD (S2FCD). Each subtype shows internal consistency in the transcriptome, genome, and phenome. The spectrum of morphometric, phenotypic, and functional changes within the "living biobank" reveals distinct differences between the molecular subtypes. Drug screens reverse subtype-specific phenotypes, suggesting phenotyped-genotyped CD PDOs can bridge basic biology and patient trials by enabling preclinical phase "0" human trials for personalized therapeutics.

INTRODUCTION: A large proportion of patients with inflammatory bowel disease (IBD) experience IBD-related inflammatory conditions outside of the gastrointestinal tract, termed extraintestinal manifestations (EIMs) which further decreases quality of life and, in extreme cases, can be life threatening. The pathogenesis of EIMs remains unknown, and although gut microbiota alterations are a well-known characteristic of patients with IBD, its relationship with EIMs remains sparsely investigated. This study aimed to compare the gut microbiota of patients with IBD with and without EIMs. METHODS: A total of 131 Danish patients with IBD were included in the study, of whom 86 had a history of EIMs (IBD-EIM) and 45 did not (IBD-C). Stool samples underwent 16S rRNA sequencing. Amplicon sequence variants (ASVs) were mapped to the Silva database. Diversity indices and distance matrices were compared between IBD-EIM and IBD-C. Differentially abundant ASVs were identified using a custom multiple model statistical analysis approach, and modules of co-associated bacteria were identified using sparse correlations for compositional data (SparCC) and related to patient EIM status. RESULTS: Patients with IBD and EIMs exhibited increased disease activity, body mass index, increased fecal calprotectin levels and circulating monocytes and neutrophils. Microbiologically, IBD-EIM exhibited lower fecal microbial diversity than IBD-C (Mann-Whitneys test, p = .01) and distinct fecal microbiota composition (permutational multivariate analysis of variance; weighted UniFrac, R2 = 0.018, p = .01). A total of 26 ASVs exhibited differential relative abundances between IBD-EIM and IBD-C, including decreased Agathobacter and Blautia and increased Eggerthella lenta in the IBD-EIM group. SparCC analysis identified 27 bacterial co-association modules, three of which were negatively related to EIM (logistic regression, p

BACKGROUND: Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. METHODS: We conducted a survival analysis of Womens Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). RESULTS: Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). CONCLUSIONS: Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a progressive immune-mediated liver disease, for which no medical therapy has been shown to slow disease progression. However, the horizon for new therapies is encouraging, with several innovative clinical trials in progress. Despite these advancements, there is considerable heterogeneity in the outcomes studied, with lack of consensus as to what outcomes to measure, when to measure and how to measure. Furthermore, there has been a paradigm shift in PSC treatment targets over recent years, moving from biochemistry-based endpoints to histological assessment of liver fibrosis, imaging-based biomarkers and patient-reported outcome measures. The abundance of new interventional trials and evolving endpoints pose opportunities for all stakeholders involved in evaluating novel therapies. To this effect, there is a need to harmonise measures used in clinical trials through the development of a core outcome set (COS). METHODS AND ANALYSIS: Synthesis of a PSC-specific COS will be conducted in four stages. Initially, a systematic literature review will be performed to identify outcomes previously used in PSC trials, followed by semistructured qualitative interviews conducted with key stakeholders. The latter may include patients, clinicians, researchers, pharmaceutical industry representatives and healthcare payers and regulatory agencies, to identify additional outcomes of importance. Using the outcomes generated from the literature review and stakeholder interviews, an international two-round Delphi survey will be conducted to prioritise outcomes for inclusion in the COS. Finally, a consensus meeting will be convened to ratify the COS and disseminate findings for application in future PSC trials. ETHICS AND DISSEMINATION: Ethical approval has been granted by the East Midlands-Leicester Central Research Ethics Committee (Ref: 24/EM/0126) for this study. The COS from this study will be widely disseminated including publication in peer-reviewed journals, international conferences, promotion through patient-support groups and made available on the Core Outcomes Measurement in Effectiveness Trials (COMET) database. TRIAL REGISTRATION NUMBER: 1239.

BackgroundAutoimmune diseases have been linked to an increased risk of pregnancy-related complications. A family history of autoimmune diseases may be related to the risk of childhood cancer based on similar histocompatibility antigens. We utilized data from national registries in Denmark to examine associations between maternal autoimmune disease and cancer in their offspring.MethodsWe linked data from several national registries in Denmark to identify childhood cancer cases in children

ObjectivesVedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC.MethodsWe performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk.ResultsOur cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness.ConclusionsUST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.

BackgroundHigher diet quality has been associated with lower risk of developing inflammatory bowel disease, but associations between diet and gastrointestinal (GI) inflammation in healthy adults prior to disease onset are understudied.ObjectivesThe purpose of this project was to examine associations between reported dietary intake and markers of GI inflammation in a healthy adult human cohort.MethodsIn a cross-sectional observational trial of 358 healthy adults, participants completed ≤3 unannounced 24-h dietary recalls using the Automated Self-Administered Dietary Assessment Tool and a Block 2014 Food Frequency Questionnaire to assess recent and habitual intake, respectively. Those who provided a stool sample were included in this analysis. Inflammation markers from stool, including calprotectin, neopterin, and myeloperoxidase, were measured by ELISA along with LPS-binding protein from plasma.ResultsRecent and habitual fiber intake was negatively correlated with fecal calprotectin concentrations (n = 295, P = 0.011, 0.009). Habitual soluble fiber intake was also negatively correlated with calprotectin (P = 0.01). Recent and habitual legume and vegetable intake was negatively correlated with calprotectin (P = 0.013, 0.026, 0.01, 0.009). We observed an inverse correlation between recent Healthy Eating Index (HEI) scores and calprotectin concentrations (n = 295, P = 0.026). Dietary Inflammatory Index scores were calculated and positively correlated with neopterin for recent intake (n = 289, P = 0.015). When participants with clinically elevated calprotectin were excluded, recent and habitual fiber, legume, vegetable, and fruit intake were negatively correlated with calprotectin (n = 253, P = 0.00001, 0.0002, 0.045, 0.001, 0.009, 0.001, 0.004, 0.014). Recent total HEI score was inversely correlated with subclinical calprotectin (P = 0.003).ConclusionsHigher diet quality may be protective against GI inflammation even in healthy adults. This trial was registered at clinicaltrials.gov as NCT02367287.

Structural repair of the intestinal epithelium is strongly correlated with disease remission in inflammatory bowel disease (IBD); however, ulcer healing is not addressed by existing therapies. To address this need, this study reports the use of a small molecule prolyl hydroxylase (PHD) inhibitor (DPCA) to upregulate hypoxia-inducible factor one-alpha (HIF-1α) and induce mammalian regeneration. Sustained delivery of DPCA is achieved through subcutaneous injections of a supramolecular hydrogel, formed through the self-assembly of PEG-DPCA conjugates. Pre-treatment of mice with PEG-DPCA is shown to protect mice from epithelial erosion and symptoms of dextran sodium sulfate (DSS)-induced colitis. Surprisingly, a single subcutaneous dose of PEG-DPCA, administered after disease onset, leads to accelerated weight gain and complete restoration of healthy tissue architecture in colitic mice. Rapid DPCA-induced restoration of the intestinal barrier is likely orchestrated by increased expression of HIF-1α and associated targets leading to an epithelial-to-mesenchymal transition. Further investigation of DPCA as a potential adjunctive or stand-alone restorative treatment to combat active IBD is warranted.

The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.

Determining the structure and phenotypic context of molecules detected in untargeted metabolomics experiments remains challenging. Here we present reverse metabolomics as a discovery strategy, whereby tandem mass spectrometry spectra acquired from newly synthesized compounds are searched for in public metabolomics datasets to uncover phenotypic associations. To demonstrate the concept, we broadly synthesized and explored multiple classes of metabolites in humans, including N-acyl amides, fatty acid esters of hydroxy fatty acids, bile acid esters and conjugated bile acids. Using repository-scale analysis1,2, we discovered that some conjugated bile acids are associated with inflammatory bowel disease (IBD). Validation using four distinct human IBD cohorts showed that cholic acids conjugated to Glu, Ile/Leu, Phe, Thr, Trp or Tyr are increased in Crohn's disease. Several of these compounds and related structures affected pathways associated with IBD, such as interferon-γ production in CD4+ T cells3 and agonism of the pregnane X receptor4. Culture of bacteria belonging to the Bifidobacterium, Clostridium and Enterococcus genera produced these bile amidates. Because searching repositories with tandem mass spectrometry spectra has only recently become possible, this reverse metabolomics approach can now be used as a general strategy to discover other molecules from human and animal ecosystems.

INTRODUCTION: Inflammatory bowel disease (IBD) is a relative contraindication to external beam radiation therapy (EBRT) for prostate cancer patients due to fear of increased risk of gastrointestinal (GI) toxicity. High-dose-rate (HDR) brachytherapy, capable of minimizing radiation dose to surrounding tissues, is a feasible alternative. Given limited data, this study examined the safety profile of HDR brachytherapy in this setting. MATERIAL AND METHODS: We conducted a retrospective review of patients with localized prostate cancer and IBD treated with HDR brachytherapy at the University of California San Francisco (UCSF), between 2010 and 2022. Eligibility criteria included biopsy-proven prostate cancer, no distant metastases, absence of prior pelvic radiotherapy, IBD diagnosis, and at least one follow-up visit post-treatment. RESULTS: Eleven patients were included, with a median follow-up of 28.7 months. The median dose administered was 2700 cGy (range, 1500-3150 cGy) over 2 fractions (range, 1-3 fractions). Two patients also received EBRT. Rectal spacers (SpaceOAR) were applied in seven patients. All patients experienced acute genitourinary (GU) toxicity, ten of which were grade 1 and one was grade 2. Eight patients experienced late grade 1 GU toxicity, and three patients had late grade 2 GU toxicity. GI toxicities were similarly low-grade, with six grade 1 acute toxicity, no grade 2 or higher acute toxicity, six grade 1 late toxicity, and one late grade 2 GI toxicity. No grade 3 or higher acute or late GI or GU toxicities were reported. CONCLUSIONS: HDR brachytherapy appears to be a safe and tolerable treatment modality for patients with prostate cancer and IBD, with minimal acute and late GI and GU toxicity. These findings warrant multi-institutional validation due to small sample size.

BACKGROUND & AIMS: Intestinal inflammation is associated with loss of enteric cholinergic neurons. Given the systemic anti-inflammatory role of cholinergic innervation, we hypothesized that enteric cholinergic neurons similarly possess anti-inflammatory properties and may represent a novel target to treat inflammatory bowel disease. METHODS: Mice were fed 2.5% dextran sodium sulfate (DSS) for 7 days to induce colitis. Cholinergic enteric neurons, which express choline acetyltransferase (ChAT), were focally ablated in the midcolon of ChAT::Cre;R26-iDTR mice by local injection of diphtheria toxin before colitis induction. Activation of enteric cholinergic neurons was achieved using ChAT::Cre;R26-ChR2 mice, in which ChAT+ neurons express channelrhodopsin-2, with daily blue light stimulation delivered via an intracolonic probe during the 7 days of DSS treatment. Colitis severity, ENS structure, and smooth muscle contractility were assessed by histology, immunohistochemistry, quantitative polymerase chain reaction, organ bath, and electromyography. In vitro studies assessed the anti-inflammatory role of enteric cholinergic neurons on cultured muscularis macrophages. RESULTS: Ablation of ChAT+ neurons in DSS-treated mice exacerbated colitis, as measured by weight loss, colon shortening, histologic inflammation, and CD45+ cell infiltration, and led to colonic dysmotility. Conversely, optogenetic activation of enteric cholinergic neurons improved colitis, preserved smooth muscle contractility, protected against loss of cholinergic neurons, and reduced proinflammatory cytokine production. Both acetylcholine and optogenetic cholinergic neuron activation in vitro reduced proinflammatory cytokine expression in lipopolysaccharide-stimulated muscularis macrophages. CONCLUSIONS: These findings show that enteric cholinergic neurons have an anti-inflammatory role in the colon and should be explored as a potential inflammatory bowel disease treatment.

Bile acids (BAs) affect the intestinal environment by ensuring barrier integrity, maintaining microbiota balance, regulating epithelium turnover, and modulating the immune system. As a master regulator of BA homeostasis, farnesoid X receptor (FXR) is severely compromised in patients with inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). At the front line, gut macrophages react to the microbiota and metabolites that breach the epithelium. We aim to study the role of the BA/FXR axis in macrophages. This study demonstrates that inflammation-induced epithelial abnormalities compromised FXR signaling and altered BAs' profile in a mouse CAC model. Further, gut macrophage-intrinsic FXR sensed aberrant BAs, leading to pro-inflammatory cytokines' secretion, which promoted intestinal stem cell proliferation. Mechanistically, activation of FXR ameliorated intestinal inflammation and inhibited colitis-associated tumor growth, by regulating gut macrophages' recruitment, polarization, and crosstalk with Th17 cells. However, deletion of FXR in bone marrow or gut macrophages escalated the intestinal inflammation. In summary, our study reveals a distinctive regulatory role of FXR in gut macrophages, suggesting its potential as a therapeutic target for addressing IBD and CAC.

Glycoprotein 2 (GP2) is a widely distributed protein in the digestive tract, contributing to mucosal barrier maintenance, immune homeostasis, and antigen-specific immune response, while also being linked to inflammatory bowel disease (IBD) pathogenesis. This review sheds light on the extensive distribution of GP2 within the gastrointestinal tract and its intricate interplay with the immune system. Furthermore, the significance of GP2 autoantibodies in diagnosing and categorizing IBD is underscored, alongside the promising therapeutic avenues for modulating GP2 to regulate immunity and maintain mucosal balance.

Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the folds (APF) is a much rarer entity that was recently recognized to occur in the setting of chronic anti-TNF therapy and inflammatory bowel disease, with 12 existing cases in the literature. Amicrobial pustulosis of the folds is a neutrophilic dermatosis characterized by aseptic pustules involving the major and minor skin folds, genital regions, and scalp. Herein, we report an additional case of paradoxical APF induced by chronic infliximab therapy in a patient with Crohn disease.

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

Background & aimsChronic inflammatory illnesses are debilitating and recurrent conditions associated with significant comorbidities, including an increased risk of developing cancer. Extensive tissue remodeling is a hallmark of such illnesses, and is both a consequence and a mediator of disease progression. Despite previous characterization of epithelial and stromal remodeling during inflammatory bowel disease, a complete understanding of its impact on disease progression is lacking.MethodsA comprehensive proteomic pipeline using data-independent acquisition was applied to decellularized colon samples from the Muc2 knockout (Muc2KO) mouse model of colitis for an in-depth characterization of extracellular matrix remodeling. Unique proteomic profiles of the matrisomal landscape were extracted from prepathologic and overt colitis. Integration of proteomics and transcriptomics data sets extracted from the same murine model produced network maps describing the orchestrating role of matrisomal proteins in tissue remodeling during the progression of colitis.ResultsThe in-depth proteomic workflow used here allowed the addition of 34 proteins to the known colon matrisomal signature. Protein signatures of prepathologic and pathologic colitic states were extracted, differentiating the 2 states by expression of small leucine-rich proteoglycans. We outlined the role of this class and other matrisomal proteins in tissue remodeling during colitis, as well as the potential for coordinated regulation of cell types by matrisomal ligands.ConclusionsOur work highlights a central role for matrisomal proteins in tissue remodeling during colitis and defines orchestrating nodes that can be exploited in the selection of therapeutic targets.

Type I interferons (IFNs) exert a broad range of biological effects important in coordinating immune responses, which have classically been studied in the context of pathogen clearance. Yet, whether immunomodulatory bacteria operate through IFN pathways to support intestinal immune tolerance remains elusive. Here, we reveal that the commensal bacterium, Bacteroides fragilis, utilizes canonical antiviral pathways to modulate intestinal dendritic cells (DCs) and regulatory T cell (Treg) responses. Specifically, IFN signaling is required for commensal-induced tolerance as IFNAR1-deficient DCs display blunted IL-10 and IL-27 production in response to B. fragilis. We further establish that IFN-driven IL-27 in DCs is critical in shaping the ensuing Foxp3+ Treg via IL-27Rα signaling. Consistent with these findings, single-cell RNA sequencing of gut Tregs demonstrated that colonization with B. fragilis promotes a distinct IFN gene signature in Foxp3+ Tregs during intestinal inflammation. Altogether, our findings demonstrate a critical role of commensal-mediated immune tolerance via tonic type I IFN signaling.

Mesenchymal stem cells (MSCs) are novel therapeutics for the treatment of Crohn's disease. However, their mechanism of action is unclear, especially in disease-relevant chronic models of inflammation. Thus, we used SAMP-1/YitFc (SAMP), a chronic and spontaneous murine model of small intestinal inflammation, to study the therapeutic effects and mechanism of action of human bone marrow-derived MSCs (hMSC). hMSC dose-dependently inhibited naïve T lymphocyte proliferation via prostaglandin E2 (PGE2) secretion and reprogrammed macrophages to an anti-inflammatory phenotype. We found that the hMSCs promoted mucosal healing and immunologic response early after administration in SAMP when live hMSCs are present (until day 9) and resulted in a complete response characterized by mucosal, histological, immunologic, and radiological healing by day 28 when no live hMSCs are present. hMSCs mediate their effect via modulation of T cells and macrophages in the mesentery and mesenteric lymph nodes (mLN). Sc-RNAseq confirmed the anti-inflammatory phenotype of macrophages and identified macrophage efferocytosis of apoptotic hMSCs as a mechanism that explains their long-term efficacy. Taken together, our findings show that hMSCs result in healing and tissue regeneration in a chronic model of small intestinal inflammation and despite being short-lived, exert long-term effects via sustained anti-inflammatory programming of macrophages via efferocytosis.

ABSTRACT Background Aim Methods Results Conclusions The worldwide prevalence of inflammatory bowel disease (IBD) is increasing, with its potential evolution as a global disease and a consequent increase in its burden on healthcare systems. These estimates do not factor in the ‘real’ price of IBD, which, beyond curbing career aspirations, instilling social stigma, and impairing the quality of life in patients, could also significantly affect the environment.To highlight potential areas for intervention and develop management strategies aimed at minimising environmental impacts in the field of IBD over time.Various aspects of IBD care (organisation of IBD centres, diagnostics and therapeutics) are examined from an environmental sustainability perspective.Each stage, from the patient's means of transport to the hospital to the physician's diagnostic and therapeutic decisions, contribute to CO2 and waste production. Strategies to contain the environmental impact are feasible. Some are easy to implement, such as ensuring the appropriateness of the diagnostic and therapeutic pathway for patients; others need to be implemented in synergy with healthcare providers' policies and pharmaceutical companies.With an inevitable increase in the number of patient visits, endoscopies, laboratory testing, and long‐term therapeutic strategies for IBD, the clinical community should be aware of environmental concerns and investigate possible strategies to reduce the environmental impact of IBD care. [ABSTRACT FROM AUTHOR]

Ulcerative Colitis (UC) is an inflammatory disorder characterized by chronic intestinal inflammation and immune dysregulation. Despite a clear association between cellular senescence and chronic inflammation and immune dysregulation, the mechanisms underlying cellular senescence in UC remain unclear. We screened differentially expressed genes (DEGs) associated with cellular senescence in multiple UC datasets, performed immune infiltration analysis, and constructed clinical diagnostic models. Additionally, we investigated the relationship between key genes related to cellular senescence and disease remission in UC patients undergoing biologic therapy, validating their expression in a single-cell dataset. We identified six DEGs associated with cellular senescence (TWIST1, IGFBP5, MME, IFNG, ME1, FOS). Immune infiltration results indicated strong correlations of four of these genes with immune cells and pathways. Through WGCNA, GO, and KEGG analyses, we found that gene modules strongly associated with the expression of hub genes in cellular senescence were enriched in inflammation-related pathways. In the single-cell dataset, the expression of these six key genes exhibited similarities with Immune infiltration results. Additionally, we constructed a nomogram using these six genes for diagnosing UC, demonstrating good diagnostic capability and clinical efficacy. Kaplan–Meier survival analysis revealed a significant association between changes in the expression levels of these cell genes and disease remission in UC patients undergoing biologic therapy. This study utilizes bioinformatic analysis and machine learning to identify and analyze features associated with cellular senescence in multiple UC datasets. It provides insights into the role of cellular senescence in the premature onset of intestinal aging in UC and offers new perspectives for exploring novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Vascular endothelial growth factor (VEGF) is linked to inflammation and angiogenesis, indicating a possible role in inflammatory bowel disease (IBD) and its main clinical manifestations, Crohn's disease (CD) and ulcerative colitis (UC). This systematic review and meta‐analysis investigated studies assessing circulating VEGF concentrations in IBD patients and healthy controls, considering the effect of IBD type, sample type and geographical location.A systematic search identified 18 studies (28 group comparators) investigating 1741 IBD patients and 1291 controls. Data were extracted and analysed using standardized mean differences (SMD) with 95% confidence intervals (CI).VEGF concentrations were significantly higher in IBD patients (SMD = .71, 95% CI .38 to 1.04; p < .001). UC patients showed higher VEGF concentrations than CD patients. Serum samples indicated significant VEGF elevations, unlike plasma samples. Significant VEGF increases were observed in studies conducted in Western Europe and Asia, but not in Eastern Europe. No significant differences were found between active and inactive disease.VEGF concentrations are elevated in IBD patients, with variations by disease type, sample type and geography. However, VEGF is not a reliable marker of disease activity. Future research should standardize methods and explore regional influences to enhance VEGF's clinical utility as a biomarker of IBD. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, and its etiology remains unclear. Presently, main drugs such as aminosalicylic acid, glucocorticoid, immunosuppressive and biological agents are employed to treat IBD. However, because of the long-term use of medication, it adversely affects other human organs. Therefore, natural bioactive compounds are applied as supplements or alternative drugs to alleviate IBD. As a kind of plant natural compounds with strong antioxidant and anti-inflammatory activities, carotenoids have exhibited potent effects in reducing intestinal inflammation. However, direct oral administration of carotenoids might cause the low specificity of inflammatory sites, which is attributed to its poor aqueous solubility and limited stability. The construction of nutrient delivery system has become an effective, efficient and dependable means. This review summarizes the delivery systems loaded with carotenoids, explores their mechanism and applications in alleviating IBD, and aims to provide corresponding theoretical references for developing novel delivery systems and their practical prospects in IBD. [ABSTRACT FROM AUTHOR]

Background: Histology has prognostic value in ulcerative colitis (UC). However, direct comparisons of histological endpoints are lacking. Aim: To perform a network meta‐analysis (NMA) to compare histological endpoints with biologics and small molecules. Methods: We searched four databases up until July 2024 for randomised controlled trials (RCTs) on advanced therapies for moderate‐to‐severe UC reporting histological endpoints. Outcomes included histological improvement or remission, and histo‐endoscopic improvement after induction or during maintenance. We used a random‐effects frequentist model and have reported outcomes as relative risk and 95% confidence interval. We estimated relative drug efficacy with the P‐score. We conducted subgroup analysis by trial phase and evaluated risk of bias and evidence certainty. Results: We included 24 RCTs (15 therapies, 8874 patients). Nineteen provided data on induction and 10 on maintenance; outcome definitions were similar. Etrasimod 2 mg/day ranked highest in achieving histologic improvement (P‐score 0.98) and remission (P‐score 0.90) following induction. Globally, guselkumab 200–400 mg ranked first for histo‐endoscopic improvement, while etrasimod 2 mg/day and upadacitinib 45 mg/day were superior in the subgroup analysis. During maintenance, upadacitinib 30 mg/day was superior in achieving histologic improvement and remission (P‐score 0.88 for both) and histo‐endoscopic improvement (P‐score 0.94). Etrasimod 2 mg/day ranked second for histologic remission (P‐score 0.70) and histo‐endoscopic improvement (P‐score 0.73), while mirikizumab 200 mg/month ranked second for histologic improvement. Conclusion: These results support the ability of small molecules to achieve stringent endpoints in moderate‐to‐severe UC. Histological outcome data for biologics was sparser, particularly during maintenance. Head‐to‐head RCTs are imperative to better inform clinical practice. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) poses a significant and growing global health challenge, affecting both humans and domestic cats. Research on feline IBD has not kept pace with its widespread prevalence in human populations. This study aimed to develop a model of feline IBD by incorporating dextran sulfate sodium (DSS) to evaluate the therapeutic potential of MSCs and to elucidate the mechanisms that enhance their action. Methods: We conducted a comprehensive clinical assessment, including magnetic resonance imaging (MRI), endoscopy, and histopathological examination. Additionally, alterations in intestinal microbiota were characterized by 16 S rDNA sequencing, and the influence of MSCs on IBD-related gene expression was investigated through transcriptome analysis. Results: According to our findings, MSC treatment significantly mitigated DSS-induced clinical manifestations, reduced inflammatory cell infiltration, decreased the production of inflammatory mediators, and promoted mucosal repair. Regarding the intestinal microbiota, MSC intervention effectively corrected the DSS-induced dysbiosis, increasing the presence of beneficial bacteria and suppressing the proliferation of harmful bacteria. Transcriptome analysis revealed the ability of MSCs to modulate various inflammatory and immune-related signaling pathways, including cytokine-cytokine receptor interactions, TLR signaling pathways, and NF-κB pathways. Conclusion: The collective findings indicate that MSCs exert multifaceted therapeutic effects on IBD, including the regulation of intestinal microbiota balance, suppression of inflammatory responses, enhancement of intestinal barrier repair, and modulation of immune responses. These insights provide a solid scientific foundation for employing MSCs as an innovative therapeutic strategy for IBD and pave the way for future clinical explorations. [ABSTRACT FROM AUTHOR]

Background: Since 2015, an infliximab biosimilar, CT-P13, has been approved for commercial use in many countries, easing the economic burden borne by society and patients. Many clinical trials investigating CT-P13 for the treatment of IBD have been conducted and reported that it may be a substitute for infliximab. However, the differences between the efficacy of CT-P13 and infliximab-originator require further elucidation. Methods: Data on the rates of clinical response, clinical remission, and mucosal healing of IBD were pooled for random-effects model meta-analysis using Stata MP 17. A total of 30 studies were included. Results: The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were naïve to biologics at 08–14 weeks were 0.66 (95% CI, 0.58–0.75) and 0.48 (95% CI, 0.43–0.54), respectively, and at 100–104 weeks were 0.66 (95% CI, 0.49 to 0.84) and 0.71 (95% CI, 0.62 to 0.79) respectively. The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were transitioned from the original agent at 24–32 weeks were 0.84 (95% CI, 0.77–0.92) and 0.78 (95% CI, 0.63–0.93), respectively, and at 48–54 weeks were 0.72 (95% CI, 0.62 to 0.82) and 0.78 (95% CI, 0.71 to 0.86) respectively. The pooled rates for mucosal healing in ulcerative colitis were 0.56 (95% CI: 0.46 to 0.67) at 08–14 weeks, and 0.64 (95% CI: 0.42 to 0.85) at 48–54 weeks. RCT studies showed no significant change in efficacy after switching, whether Crohn's disease or ulcerative colitis. Conclusions: CT-P13 is effective in short and long-term periods. The application of CT-P13 for the management of IBD was promising. [ABSTRACT FROM AUTHOR]

Background: Many women of childbearing age with inflammatory bowel disease (IBD) require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules tofacitinib, filgotinib, upadacitinib and ozanimod (TFUO) have shown concerning teratogenic effects, and decreased fertility in animal studies. Therefore, their use in women of childbearing age needs careful consideration. Design: RAND/University of California Los Angeles (UCLA) Appropriateness Method (RAM). Objective: To evaluate the appropriateness of TFUO in women of childbearing age. Methods: We convened a panel of six gastroenterologists, two IBD nurses, one IBD pharmacist and three expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds. Results: All 13 statements were deemed appropriate. The panel concluded that women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception and be counselled regarding the risk in unplanned pregnancies. For women using contraception while on Janus kinase inhibitor (JAKi) therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception. TFUO are contraindicated during pregnancy and breast feeding. We recommend that women receiving TFUO cease therapy in time to establish clinical remission for at least 3 months prior to conception. Therapies other than TFUO should be considered as first-line therapy in women with IBD of childbearing age, except in select individual circumstances. TFUO may be appropriate for women of childbearing age after failure of, intolerance or contraindications to one biological agent. Conclusion: TFUO should be avoided during pregnancy and breastfeeding, and alternative therapies should be considered as first-line treatments. Summary: We provide clinical practice recommendations regarding the use of TFUO for IBD in women of childbearing age. Plain language summary: Small Molecules for Patients with IBD of Childbearing Age The maintenance of remission is vital for good fetal and maternal outcomes in IBD pregnancies and biological therapies used in IBD have been associated with favourable pregnancy outcomes. The safety profile of novel small molecules in human pregnancy is however largely unknown. We conducted a RAND appropriateness panel to agree recommendation son the use of Tofacitinib, Filgotinib, Upadacitinib and Ozanimod in women of childbearing age. Tofacitinib, Filgotinib, Upadacitinib and Ozanimod should be avoided during pregnancy due to serious concerns regarding birth defects. Small molecule therapies Tofacitinib, Filgotinib, Upadacitinib and Ozanimod should be given due consideration in the management of IBD in women of childbearing age, provided there are no immediate plans for conception. Counselling about potential risk of adverse effects during pregnancy, risk of venous thromboembolism and effective contraception are needed. Clinicians need to consider time to establish alternative therapies when switching away from Tofacitinib, Filgotinib, Upadacitinib and Ozanimod in the pre-conception period. Future research should examine pregnancy outcomes in cases where Tofacitinib, Filgotinib, Upadacitinib and Ozanimod exposure occurred but data may be difficult to compare to biologics due to differences in exposure duration. Guidelines should be updated as further maternal and fetal safety data become available [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusions The number of adults aged over 60 years with inflammatory bowel disease (IBD) is increasing. Frailty, rather than chronological age, may be a better predictor of adverse health outcomes.To summarise current knowledge about frailty in adults with IBD including the prevalence and associations of frailty and IBD‐related adverse outcomes.We performed an electronic search of MEDLINE, EMBASE and EMBASE Classic databases using search terms for IBD and frailty from inception to 14 February 2024. All studies involving adults aged ≥ 16 with a confirmed diagnosis of IBD that included a frailty assessment were eligible for inclusion.We included 23 observational studies involving 1,893,448 adults. Risk of bias was low for 18 studies and moderate for five. Twelve methods of frailty assessment were used, the most common being the Hospital Frailty Risk Score. Pooled prevalence of frailty in IBD patients was 18% (95% confidence interval (CI) 12.4%–25.6%). Meta‐analysis of unadjusted events data demonstrated that frailty increased the risk of infection‐related admissions following treatment in two studies (relative risk (RR) 1.9; 95% CI 1.2–3.0), post‐operative morbidity in three (RR 2.0; 95% CI 1.4–2.7) and mortality in seven (RR 4.3; 95% CI 2.6–7.4).Frailty is common in patients with IBD and is associated with IBD‐related adverse outcomes including infection‐related admissions following treatment, post‐operative morbidity and death. Future work should focus on developing risk assessment tools to better support decision making for older people with frailty and IBD. [ABSTRACT FROM AUTHOR]

Background: The intestinal epithelial barrier is the first line of defense against pathogens and noxious substances entering the body from the outside world. Through proliferation and differentiation, intestinal stem cells play vital roles in tissue regeneration, repair, and the maintenance of intestinal homeostasis. Inflammatory bowel disease (IBD) is caused by the disruption of intestinal homeostasis through the invasion of toxic compounds and pathogenic microorganisms. Hylotelephium erythrostictum (Miq.) H. Ohba (H. erythrostictum) is a plant with diverse pharmacological properties, including antioxidant, anti-inflammatory, antidiabetic, and antirheumatic properties. However, the roles of H. erythrostictum and its bioactive compounds in the treatment of intestinal injury are unknown. Methods: We examined the protective effects of H. erythrostictum water extract (HEWE) and H. erythrostictum butanol extract (HEBE) on Drosophila intestinal injury caused by dextran sodium sulfate (DSS) or Erwinia carotovoracarotovora 15 (Ecc15). Results: Our findings demonstrated that both HEWE and HEBE significantly prolonged the lifespan of flies fed toxic compounds, reduced cell mortality, and maintained intestinal integrity and gut acid‒base homeostasis. Furthermore, both HEWE and HEBE eliminated DSS-induced ROS accumulation, alleviated the increases in antimicrobial peptides(AMPs) and intestinal lipid droplets caused by Ecc15 infection, and prevented excessive ISC proliferation and differentiation by inhibiting the JNK, EGFR, and JAK/STAT pathways. In addition, they reversed the significant changes in the proportions of the gut microbiota induced by DSS. The bioactive compounds contained in H. erythrostictum extracts have sufficient potential for use as natural therapeutic agents for the treatment of IBD in humans. Conclusion: Our results suggest that HEWE and HEBE are highly effective in reducing intestinal inflammation and thus have the potential to be viable therapeutic agents for the treatment of gut inflammation. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]

Introduction and aim. Orthorexia nervosa is described as an obsession with consuming solely healthy foods accompanied by restrictive behaviors. Patients with chronic conditions frequently require dietary interventions alongside medication to manage symptoms and slow down disease progression. However, when dietary restrictions are taken to extremes, individuals may develop orthorexia nervosa, resulting in malnutrition and weight loss. This poses risks during treatment, where maintaining a balanced diet is vital. In this review we aim to display the prevalence of orthorexia nervosa in patients suffering from selected chronic diseases. Material and methods. A literature review was performed to investigate the prevalence of orthorexia nervosa among individuals with type 1 diabetes, inflammatory bowel disease, celiac disease, rheumatoid arthritis, and cancer. Description of the State of Knowledge. The occurrence of orthorexia reaches up to 7% in the general population, 72% in patients with type 1 diabetes mellitus, 77% in case of inflammatory bowel disease, 71% among individuals suffering from celiac disease, 75% in those with rheumatoid arthritis, and 50% in case of cancer. Orthorexia nervosa predominantly affects females who are younger, have higher levels of education, select organic foods, prepare their own meals, and have other concurrent chronic illnesses. The distress associated with diagnosis is considered the primary factor contributing to the development of this condition. Orthorexia ultimately leads to malnutrition, weight loss, impaired social functioning, and poses a risk of complications during the management of patients suffering from chronic diseases. Conclusion. The prevalence of orthorexia nervosa in patients suffering from the exhibited chronic illnesses is significantly higher compared to the general population. Therefore, early detection of this condition and intervention are necessary to improve patient management. Further research is needed to assess the frequency of orthorexia among individuals suffering from other chronic diseases. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Despite advancements in therapeutic options for Crohn's disease (CD), strictureplasty is a mainstay bowel‐preserving technique for small bowel CD. We sought to audit international practice across three high‐volume centres since the widespread use of biologic medication.A retrospective audit was performed for all strictureplasties undertaken for small bowel CD, over a 15‐year period (2006–2021), in three high‐volume centres in the United Kingdom and Italy. Primary endpoints were clinical recurrence and reoperation for recurrence.In all, 123 patients were included; 58% were men, 25% smoked and 60% had previous abdominal surgery for CD. Median age was 40 years (interquartile range 30–52 years), mean body mass index 22 (15–31) and median disease duration 138 months (81–255 months). 42% had been treated with biologics preoperatively. In total 338 strictureplasties were performed in 123 patients, with a median of two per patient (interquartile range 1–3). Complications occurred in 35%, with 8% scoring Clavien–Dindo Grade 3. There were no Grade 4/5 complications. Postoperative biologic treatment was administered to 84/123 patients (68.3%). Median follow‐up was 54 months. 41/123 patients (33.3%) developed clinical recurrence. Reoperation for recurrent stricturing was performed in 26/123 patients (21%). Clinical recurrence and reoperation rates were significantly higher in patients who continued to smoke after their index surgery.Strictureplasty remains a safe and effective surgical treatment for small bowel CD. Recurrence and reoperation rates remain high, regardless of postoperative biologic therapy. Smoking significantly increases the risk of recurrence. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation, progressive bowel damage and gastrointestinal lesions. Although treatment strategies for CD have traditionally focused on a stepwise pharmacological approach to achieve clinical remission or symptom resolution, these treatment goals correlate poorly with disease activity. Thus, achieving full clinical remission and full endoscopic healing alone may be insufficient, as patients may remain at risk of inflammatory complications. Individualised 'treat-to-target' (T2T) pharmacological and treatment approaches represent a promising strategy for improving endoscopic remission and symptom resolution among patients with CD. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II guidelines, launched in 2013 and later renewed, identified individualised targets for a T2T therapeutic approach for patients with IBD. These guidelines facilitate the individualisation of target treatment goals through evidence-based, long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article aims to summarise the STRIDE-II guidelines and provide intellectual guidance for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the United Kingdom (UK). Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice. Declaration of interest: This article was commissioned and funded by Takeda UK Ltd, who suggested the author and topic. Takeda UK Ltd also reviewed and approved the content. Prescribing information and adverse event reporting can be found at the end of the article. Plain language summary: Best practice suggestions for incorporating STRIDE-II into UK clinical practice for the management of patients with Crohn's disease Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) characterised by endoscopic inflammation and damage, estimated to affect approximately 11 individuals per 100,000 annually in the United Kingdom (UK). Traditional treatment strategies for IBD, including CD, focus on symptom resolution and clinical remission. However, as symptom resolution correlates poorly with disease activity, a treatment goal of full clinical remission and full endoscopic healing alone may be insufficient. The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) and STRIDE-II initiative released 'treat-to-target' therapy evidence-based guidelines, detailing individualised clinical treatment targets for patients with IBD. STRIDE-II accommodates treatment individualisation through several long-term (health-related quality of life, absence of disability, endoscopic healing) and intermediate/short-term (abdominal pain, stool frequency, normalisation of biomarker levels) treatment targets, allowing patients and clinicians to consider the risk-to-benefit balance of goals and selected therapeutic strategies. This article provides best practice suggestions for healthcare professionals to apply the STRIDE-II principles to current clinical practice in the UK. Management recommendations for primary and secondary first-line non-responders are provided, along with suggestions for utilising the endoscopic outcomes scoring system in UK clinical practice. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a disorder causing chronic inflammation in the gastrointestinal tract, and its pathophysiological mechanisms are still under investigation. Here, we find that mice deficient of YOD1, a deubiquitinating enzyme, are highly susceptible to dextran sulfate sodium (DSS)-induced colitis. The bone marrow transplantation experiment reveals that YOD1 derived from hematopoietic cells inhibits DSS colitis. Moreover, YOD1 exerts its protective role by promoting nucleotide-binding oligomerization domain 2 (NOD2)-mediated physiological inflammation in macrophages. Mechanistically, YOD1 inhibits the proteasomal degradation of receptor-interacting serine/threonine kinase 2 (RIPK2) by reducing its K48 polyubiquitination, thereby increasing RIPK2 abundance to enhance NOD2 signaling. Consistently, the protective function of muramyldipeptide, a NOD2 ligand, in experimental colitis is abolished in mice deficient of YOD1. Importantly, YOD1 is upregulated in colon-infiltrating macrophages in patients with colitis. Collectively, this study identifies YOD1 as a novel regulator of colitis. Synopsis: NOD2-mediated physiological inflammation is critical for maintaining intestinal homeostasis. The deubiquitinating enzyme YOD1 potentiates protective NOD2 signaling by stabilizing RIPK2, thereby ameliorating intestinal inflammation and colitis. Deficiency of YOD1 in hematopoietic cells exacerbates DSS-induced experimental colitis in mice. YOD1 is highly expressed in mucosa-infiltrating macrophages and potentiates inflammatory responses in macrophages. YOD1 enhances NOD2 signaling by stabilizing RIPK2 through K48 deubiquitylation. NOD2-mediated physiological inflammation is critical for maintaining intestinal homeostasis. The deubiquitinating enzyme YOD1 potentiates protective NOD2 signaling by stabilizing RIPK2, thereby ameliorating intestinal inflammation and colitis. [ABSTRACT FROM AUTHOR]

Treatment of inflammatory bowel disease (IBD), a common chronic intestinal disease, by exopolysaccharides (EPSs) produced by lactic acid bacteria has raised increasing concerns. Here, the EPS produced by Lactiplantibacillus plantarum NMGL2 was evaluated for its ameliorating effect on dextran sodium sulfate (DSS)-induced IBD in mice. Administration of the EPS was shown to decrease the body weight loss and the values of disease activity index (DAI) and alleviate the colon damage as evidenced by an improvement in colonic length shortening, a reduction in colonic coefficient, and a reduction in colonic mucosal architecture and inflammatory infiltration. Cytokine assay of the blood and colon tissue samples showed that the EPS could decrease the levels of pro-inflammatory TNF-α and IL-1β, and increase anti-inflammatory IL-10. Oxidative stress assay of the colon tissue showed that the nitric oxide (NO) and malondialdehyde (MDA) levels decreased significantly (p < 0.05), while superoxide dismutase (SOD) and glutathione (GSH) levels increased significantly (p < 0.05) after the EPS intervention. These results were further confirmed by the significantly (p < 0.05) down-regulated levels of NF-κB p65, p-IKKβ, and p-IκBα, and significantly (p < 0.05) enhanced expression of ZO-1 and occludin, as evaluated by Western-blot analysis of these proteins expressed in colonic tissue. The EPS produced by L. plantarum NMGL2 alleviated IBD by suppressing the NF-κB signaling pathway, suggesting its potential as a functional food agent in the prevention of IBD. [ABSTRACT FROM AUTHOR]

Background: Homocysteine (Hcy) is a pro-inflammatory molecule that has the potential to induce oxidative damage to cells and stimulate the release of inflammatory mediators. Hcy has been observed to enhance the production of inflammatory agents in vascular endothelial cells. However, the impact of Hcy on intestinal mucosal inflammation remains largely unexplored. Therefore, the objective of this study was to examine the potential of Hcy to stimulate the synthesis of inflammatory mediators and elucidate the underlying mechanisms in the intestinal mucosa. Methods: A total of 99 patients diagnosed with inflammatory bowel disease (IBD) and 10 healthy individuals were included in this study to assess the impact of homocysteine (Hcy) on the levels of leukotriene E4 (LTE4) and prostaglandin E2 (PGE2). The underlying mechanism responsible for the generation of LTE4 and PGE2 induced by Hcy was investigated using colitis rats and Caco-2 cells. 32 Sprague–Dawley rats were categorized into four groups: normal control, TNBS model, normal with Hcy injection, and TNBS model with Hcy injection. The mRNA expressions of 5-LOX, COX-2, and NF-κB were assessed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Caco-2 cells were subjected to treatment with varying concentrations (10, 20, 50, 100 μmol/L) of Hcy and incubated for different durations (1, 3, 6 h). The alterations in NF-κB activity, as well as the levels of Hcy, LTE4, and PGE2, were measured using enzyme-linked immunosorbent assay (ELISA). Results: The excretion of Hcy, LTE4, and PGE2 in urine exhibited significant increases in patients with inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC). In addition, Hcy demonstrated a significant increase in the expression of 5-LOX, COX-2, and NF-κB, as well as elevated levels of LTE4 and PGE2 in rats with colitis. Furthermore, Hcy was found to induce NF-κB activation and nuclear translocation, thereby contributing to the enhanced synthesis of LTE4 and PGE2 in Caco-2 cells. Conclusions: Hcy was found to enhance the expression of 5-LOX and COX-2 by activating NF-κB, thereby augmenting the production of LTE4 and PGE2, which ultimately exacerbates colonic inflammation in individuals with inflammatory bowel disease (IBD). [ABSTRACT FROM AUTHOR]

Background: Opioid use is non-trivial in children with inflammatory bowel disease (IBD) and arthritis, and options are limited for pain management. We aimed to determine the impacts of chronic opioid use on acute care utilization in children with both IBD and arthritis in United States. Methods: Participants less than 18 years of age with IBD and arthritis, with at least one year of continuous enrollment (no interruption of insurance for at least 1 year) and at least one pharmacy claim in the Truven Health MarketScan Claims and Encounter Database, were included in the study. The primary exposure was chronic opioid use. Chronic opioid users were matched to non-exposed controls. The primary outcome was acute healthcare utilization (total number of emergency department visits and hospitalizations within 12–24 months after the index date). The association between acute care utilization and chronic opioid use was assessed using a multivariable negative binomial regression model. Results: 480 children with IBD and arthritis met inclusion criteria, out of which 59 (12.3%) met the criteria for chronic opioid exposure, and 46 of them had at least one year of follow-up. IRR (incidence rate ratio) of acute healthcare use for patients exposed to chronic opioid use was 1.7 higher than controls. Additionally, public insurance and having a chronic pain condition were independently and significantly associated with greater acute healthcare use. Conclusion: Chronic opioid use was significantly associated with greater acute health care utilization in children with IBD and arthritis than matched unexposed controls. Future investigation is warranted to determine if preferential use of non-opioid therapy for pain control can reduce acute healthcare costs in this population. [ABSTRACT FROM AUTHOR]

The incidence of patients diagnosed with either breast cancer (BC) or inflammatory bowel disease (IBD) is increasing each year. IBD has been shown to be strongly associated with the development of a variety of solid tumors, but the relationship with breast cancer is not yet definitive. We explored the causative relationship between IBD and BC using a Mendelian randomization (MR) strategy. MR-Egger regression, weighted median (WM), simple median (SM), maximum likelihood (ML), and inverse variance weighting (IVW) methods were among the analytical techniques used in this work. The examination of heterogeneity was conducted by the use of Cochran's Q test and Rucker's Q test. The sensitivity analysis in this study used the IVW and MR-Egger methodologies. The results of our investigation suggested that IBD had a beneficial impact on estrogen receptor-negative (ER-) breast cancer (odds ratio (OR) = 0.92, P = 0.02). The study did not find a significant association between IBD and the risk of developing overall breast cancer (OR = 0.99, P = 0.60), as well as estrogen receptor-positive (ER+) breast cancer (OR = 1.02, P = 0.60) specifically. In addition, our study findings indicated that there was a detrimental association between ER+ breast cancer and IBD as determined using reverse MR analysis (OR = 1.07, P = 0.04). Furthermore, this analysis failed to observe any significant association between overall breast cancer (OR = 1.07, P = 0.07) or ER- breast cancer (OR = 0.99, P = 0.89) and IBD. Our bidirectional MR study yielded a correlation between IBD and some specific hormone receptor status of BC. [ABSTRACT FROM AUTHOR]

Background: This study aims to analyze the historical trends of inflammatory bowel disease (IBD) burden in the elderly from 1990 to 2021 and forecast future trends up to 2051. Methods: Data from the Global Burden of Disease Study 2021 were utilized. Age-standardized rates (ASR) for incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were calculated. Estimated annual percentage changes (EAPCs) were computed to quantify temporal trends. A Bayesian Age-Period-Cohort model was employed to project future trends. Results: From 1990 to 2021, the global number of elderly IBD increased from 573,500 to 1,278,190. The age-standardized incidence rate (ASIR) rose from 8.01 to 8.77 per 100,000, while the age-standardized prevalence rate (ASPR) slightly decreased from 118.14 to 117.29 per 100,000. Death number increased from 14,400 to 33,490, but the age-standardized mortality rate decreased from 3.21 to 2.84 per 100,000. DALYs increased from 324,100 to 683,750, with the age-standardized DALYs rate declining from 68.78 to 60.88 per 100,000. Significant geographical variations were observed, with high Socio-demographic Index regions showing the highest burden. Projections suggest that by 2051, elderly IBD prevalence number may reach 2,316,000, with ASIR and ASPR potentially rising after 2035 and 2042, respectively. Deaths and DALYs are projected to increase to 75,000 and 1,401,000 respectively, despite continued declines in ASRs. Conclusion: The absolute burden of IBD in the elderly population is projected to increase substantially by 2051, despite decreasing ASRs. These findings underscore the need for tailored healthcare strategies and resource allocation to address the growing challenge of elderly IBD globally. [ABSTRACT FROM AUTHOR]

Objective: This study aims to analyze the causal relationship between autoimmune thyroiditis (AIT) and inflammatory bowel disease (IBD) using bidirectional Mendelian randomization (MR). Methods: Single nucleotide polymorphisms were obtained from FinnGen. Exposure-outcome causality was assessed using inverse variance weighted, MR-Egger, and weighted median. MR-Egger intercept, Cochran's Q, and leave-one-out sensitivity analysis were used to evaluate horizontal pleiotropy, heterogeneity, and robustness, respectively. Results: Forward analysis revealed no significant association between AIT and the risk of ulcerative colitis (UC) (odds ratio [OR] 1.008, 95% confidence interval [CI] 0.986 to 1.03, p = 0.460) or Crohn's disease (CD) (OR 0.972, 95% CI 0.935 to 1.010, p = 0.143). Reverse analysis showed that UC (OR 0.961, 95% CI 0.783 to 1.180, p = 0.707) was not associated with AIT risk, while CD (OR 2.371, 95% CI 1.526 to 3.683, p < 0.001) was linked to an increased risk of AIT. Intercept analysis and Cochran's Q test indicated no horizontal pleiotropy or heterogeneity. Sensitivity analysis confirmed the robustness of the MR results. Conclusion: This MR analysis suggests that CD, but not UC, is a risk factor for AIT, whereas AIT is not associated with the risk of IBD. Proactive prevention and treatment of CD can help mitigate the risk of AIT. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder, and its incidence of comorbid with major depressive disorder (MDD) is significantly higher than the general population. However, many patients lack proper recognition and necessary psychological health treatments. We aimed to identify potential biomarkers and mechanisms involved in the development of IBD comorbid with MDD (IBD-MDD). Methods: We utilized IBD and MDD-related datasets from the GEO database for differential gene expression analysis, protein-protein interaction (PPI) and pathway enrichment analysis, random forest algorithm, LASSO regression analysis, and construction of a disease prediction model. We assessed the accuracy of the model using ROC curve, explored potential mechanisms through immune infiltration analysis, and validated candidate biomarkers using peripheral blood samples from patients in our center's cohort. Results: We identified 484 IBD-related secreted proteins and 142 key module genes associated with MDD. PPI analysis revealed two crucial modules primarily involved in inflammation and immune regulation. We identified four diagnostic genes (HGF, SPARC, ADAM12, and MMP8) from the 21 shared genes between IBD-related secreted proteins and MDD key module genes, constructed a nomogram model and confirmed its accuracy using ROC curve from an external independent dataset. Immune infiltration analysis revealed significant associations between the four diagnostic genes, and cellular immune dysregulation in MDD. Finally, we validated the expression patterns of the four diagnostic genes in our cohort. Conclusions: Our study discovered four candidate biomarkers for IBD-MDD, providing new insights for the diagnosis and therapeutic intervention of serum-based IBD comorbid with MDD. [ABSTRACT FROM AUTHOR]

Given the unique anatomy and location of inflammatory bowel disease (IBD), oral pharmacological treatment is the mainstay for managing IBD because of its convenience and direct accessibility to the gastrointestinal tract. However, efficient delivery systems must be designed to navigate the harsh gastrointestinal environment during application. Here, an innovative oral drug delivery system was proposed using nanomotor (NM)‐loaded soluble microcapsules for treating IBD. MnO2‐Au‐mSiO2 NMs incorporate partially encapsulated MnO2 antennas that convert reactive oxygen species into oxygen, autonomously propelling the NMs. Astaxanthin (AST), known for its anti‐inflammatory properties, is loaded into the mesoporous silica (mSiO2) of NMs (AST@NMs). AST effectively reduces inflammation and shifts macrophages from a proinflammatory (M1) phenotype to an anti‐inflammatory (M2) phenotype. To protect the nanomotors from harsh digestive conditions and achieve intestinal‐responsive release, using photocurable 3D printing, we fabricated enteric‐coated oral microcapsules (MCs). Additionally, to prevent leakage of AST@NMs, a calcium alginate shell was cured in situ on the surface of the microcapsules (AST@NMs@MCs). In vitro and in vivo, AST@NMs@MCs effectively reduced inflammation, repaired the intestinal barrier, and modulated the gut microbiota. These findings underscore the protective effects of the microcapsules on AST@NM, highlighting their potential as a promising strategy for treating colitis. [ABSTRACT FROM AUTHOR]

Background Objectives Materials and Methods Results Discussion Conclusion Dietary factors and chronic gastrointestinal diseases are frequent determinants of sexual dysfunctions (SD). Whether inflammatory bowel diseases (IBD) are associated with SD is not well known as well as the role of diet and quality of life (QoL).To evaluate the prevalence of SD in a cohort of IBD patients and assess the role of clinical‐demographic variables, adherence to Mediterranean diet (MD) and QoL.This is a cross‐sectional observational study involving 301 patients (134 females and 167 males); 119 had Crohn's Disease and 182 had ulcerative colitis. SD were assessed through the Female Sexual Function Index (FSFI) and the International Index of Erectile Function (IIEF). Adherence to MD was evaluated by the MD Score. QoL was investigated by the 12‐item Short‐Form Health Survey (SF‐12) which yields summary scores of physical (PCS) and mental (MCS) health. Multiple logistic regression was used to identify predictors of SD.Prevalence of SD in females was 61.9%, while 52.1% of males had erectile dysfunction. No differences in the prevalence of SD were found between CD and UC in both males and females. IBD activity, as defined by patient‐reported outcomes, was significantly associated with SD in both sexes. In females, MD adherence score (OR 0.8, 95% CI 0.653–0.974, p = 0.027), PCS (OR = 0.936, CI 95% = 0.891–0.983, p = 0.008), and MCS (OR 0.9, 95% CI 0.906–0.985, p = 0.008) were protective against SD, whereas in males a higher PCS was associated with a lower probability of SD (OR 0.9, 95% CI 0.891–0.978, p = 0.004)IBD patients had a significant prevalence of SD which occurred more frequently in females than in males. Disease activity is associated with a higher likelihood of SD in both sexes, whereas dietary factors are differentially associated with SD in males and females. A better QoL is associated with a lower risk of SD.SD is prevalent among men and women with IBD. Adherence to MD, PCS and MCS in females as well as PCS in males were protective against SD. The assessment of sexual function in IBD patients could be relevant in order to reach an early diagnosis and a timely treatment. [ABSTRACT FROM AUTHOR]

Introduction: Observational studies have discovered a contradictory phenomenon between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between H. pylori and IBD, including ulcerative colitis (UC) and Crohn's disease (CD). Methods: We conducted a Mendelian randomization (MR) study with two sample Genome-Wide Association Studies (GWAS) to determine whether there is a causal relationship between H. pylori infection and IBD, as well as the possible pathogenic factors that may be involved. The reliability of the main MR assumptions was examined through a series of sensitivity analyses. Results: Two genetic variants (SNPs) previously identified were employed as instrumental variables (IVs) for H. pylori infection. GWAS data for IBD, UC, and CD were obtained from the recent DF10 release10 of the FinnGen study. Our findings indicated a significant association between H. pylori seropositivity and an increased risk of IBD and UC (IBD: OR: 1.16, 95% CI, 1.03–1.31, P < 0.05; UC: OR: 1.22, 95% CI, 1.08–1.37, P < 0.001) while no causal relationship with CD (P > 0.05). Analysis of the main virulence pathogenic factors revealed a causal relationship between cytotoxin-associated protein A (CagA) and IBD and UC (IBD: OR: 1. 06, 95% CI, 1.001–1.11, P < 0.05; UC: OR: 1.07, 95% CI, 1.004–1.14, P < 0.05), while no correlation was found for vacuolar cytotoxin A (VacA) (P > 0.05). After applying the False Discovery Rate (FDR) correction, the causal relationship between CagA and the risk of IBD or UC was no longer statistically significant. Conclusion: This study suggests a potential causal relationship between H. pylori infection and IBD, particularly UC. The effect may be more pronounced in individuals with previous H. pylori infections. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) causes chronic inflammation of the colon and digestive tract, and it can be classified as Crohn's disease (CD) and Ulcerative colitis (UC). IBD is more prevalent in Europe and North America, however, since the beginning of the 21st century it has been increasing in South America, Asia, and Africa, leading to its consideration as a worldwide problem. Optical colonoscopy is one of the crucial tests in diagnosing and assessing the progression and prognosis of IBD, as it allows a real-time optical visualization of the colonic wall and ileum and allows for the collection of tissue samples. The accuracy of colonoscopy procedures depends on the expertise and ability of the endoscopists. Therefore, algorithms based on Deep Learning (DL) and Convolutional Neural Networks (CNN) for colonoscopy images and videos are growing in popularity, especially for the detection and classification of colorectal polyps. The performance of this system is dependent on the quality and quantity of the data used for training. There are several datasets publicly available for endoscopy images and videos, but most of them are solely specialized in polyps. The use of DL algorithms to detect IBD is still in its inception, most studies are based on assessing the severity of UC. As artificial intelligence (AI) grows in popularity there is a growing interest in the use of these algorithms for diagnosing and classifying the IBDs and managing their progression. To tackle this, more annotated colonoscopy images and videos will be required for the training of new and more reliable AI algorithms. This article discusses the current challenges in the early detection of IBD, focusing on the available AI algorithms, and databases, and the challenges ahead to improve the detection rate. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) have an increased risk of gallstone disease. We aimed to systematically evaluate the prevalence rate and relevant risk factors of gallstones in CD patients. Methods: A comprehensive search of PubMed, Embase, and Web of Science databases from inception to September 10, 2023, identified studies investigating risk factors for gallstone development among CD patients. Gender, age, body mass index, disease duration, disease site, stenosis, prior surgery, hospitalization times, corticosteroids, immunomodulators, and total parenteral nutrition (TPN) were assessed as potential risk factors. Odds ratios (OR) and confidence intervals (CI) were calculated. Result: Among 1184 articles, 11 observational studies (3588 patients) were included. The prevalence of CD patients with gallstones was approximately 14.7%. Factors significantly associated with increased gallstone risk included Age ≥ 40 years old (OR 3.06, 95% CI 2.09- 4.48), disease duration > 15 years (OR 3.01, 95% CI 2.06–4.42), lifetime surgery(OR 2.50, 95% CI 1.99–3.12), disease located in ileocolon (OR 1.38, 95% CI 1.04–1.83) and ileocecal(OR 1.93, 95% CI 1.16–3.21), multiple hospitalizations(OR 4.26, 95% CI 2.43–7.46), corticosteroid treatments(OR 2.65, 95% CI 1.52–4.63), immunomodulator therapy(OR 1.94, 95% CI 1.12–3.38), and TPN use(OR 2.66, 95% CI 1.29–5.51). Sex, stenosis, overweight, or low weight did not significantly increase the risk of gallstone developing. Conclusion: Age, long disease duration, specific disease locations (ileocolon, ileocecal), surgery, number of hospitalizations, corticosteroids, immunomodulator therapy, and TPN were identified as factors that increased the risk of gallstones in CD patients. About 14.7% of CD patients experience gallstones, so raising awareness and implementing prevention are needed. Registration: PROSPERO (CRD42023449299). [ABSTRACT FROM AUTHOR]

Oral administration of probiotics has demonstrated substantial potential in alleviating colitis. However, most of the ingested microorganisms struggle to survive the harsh conditions of the gastrointestinal tract, leading to decreased efficacy. In the present study, using double emulsification (W1/O/W2) and complex coacervation methods, we developed a gelatin/carboxymethyl cellulose (CMC)‐based probiotic microcapsule and analyzed the efficacy of encapsulated probiotics in preventing dextran sodium sulfate (DSS)‐induced colitis in mice. Our results reveal that nearly 90% of the encapsulated probiotics remained viable after 30‐day storage at 4°C and approximately 38.1% of viable bacteria (4.0 × 108 cfu/g) survived after 4‐h simulated gastrointestinal digestion. In a DSS‐induced colitis model, pretreatment with probiotics exerted significant protective effects, with the bacterial microcapsule‐treated group having superior outcomes to those of the bacterial suspension plus empty carrier group. Probiotic treatments, especially those administered in the encapsulated form, significantly increased fecal short‐chain fatty acid contents, and altered the intestinal microbial composition. The family Muribaculaceae, dominant bacteria in the mouse gut, may be the key microorganism involved in the BM regulation process. Our study presents an alternative approach to treating colitis using probiotics. Practical Application: The encapsuled probiotic showed remarkable storage stability at 4°C, maintained good vitality after simulated digestion, and gained superior outcomes in preventing colitis. Our results offer an alternative approach for the probiotic preparations aiming to prevent the intestinal inflammation. [ABSTRACT FROM AUTHOR]

Background/Objectives: The increasing global prevalence of inflammatory bowel disease (IBD) presents significant challenges to healthcare systems. Our objective was to identify the sociodemographic and clinical characteristics of IBD patients in Catalonia. Methods: A cross-sectional analytical study was carried out on patients diagnosed with IBD in Catalonia (2021). The database of the Information System for the Development of Research in Primary Care of Catalonia was used. Results: In Catalonia, the prevalence of IBD was 474 cases per 100,000 people (pcm), with an average diagnosis age of 42.9 years. Crohn's disease (CD) represented 34.34% of cases, and 21.2% were smokers and 1% were alcoholics. Nutritional status showed 3% underweight, 36.2% overweight, and 20% obese, with only 0.27% diagnosed as malnutrition. Mental health issues are notable; 36,531 pcm patients were diagnosed with anxiety and 14,656 pcm with depression, and 8.24% had a high risk of mortality measured by the Charlson index. The most prevalent vaccine-preventable infections were influenza (19,356 pcm), herpes zoster (8099 pcm), and varicella zoster (6946 pcm), with 4.56% of patients requiring hospitalisation for one of these reasons and 32.8% of patients for IBD complications, with higher rates observed in cases of CD. Conclusions: The prevalence of IBD was high, especially in urban areas, and patients showed a relevant number of comorbidities. IBD requires a comprehensive evaluation and interdisciplinary management to improve disease control. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is associated with an increased prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). The Fibrosis-4 (FIB-4) index is a non-invasive tool for assessing liver fibrosis that has been validated in various liver diseases. The main objective of this study was to study whether the FIB-4 index is a reliable predictor of liver fibrosis, as assessed through elastography, in patients with IBD. We additionally aimed to analyze if FIB-4 associates with IBD characteristics such as lipid profile, subclinical carotid atherosclerosis, and insulin resistance indices. Methods: A cross-sectional study was conducted, enrolling 197 patients with IBD. Subjects underwent comprehensive clinical and laboratory evaluations. Hepatic fibrosis was assessed non-invasively using the FIB-4 index and transient elastography, while abdominal ultrasonography was performed to grade hepatic steatosis based on the degree of fat infiltration. To investigate the associations between disease characteristics and FIB-4 score and the correlation of this index to elastography, a multivariable linear regression analysis was conducted. Results: The presence of diabetes, hypertension, and metabolic syndrome was associated with significantly higher FIB-4 levels. However, FIB-4 did not show a relationship with disease characteristics such as phenotype or activity indices. Furthermore, FIB-4 did not demonstrate a correlation with liver stiffness values measured by elastography. Conclusions: Our findings suggest that the FIB-4 index may not be a reliable tool for assessing hepatic fibrosis in patients with IBD. This observation is particularly significant given the high prevalence of MASLD in the IBD population. [ABSTRACT FROM AUTHOR]

Background: Biologics are a cornerstone in the treatment of severe cases of inflammatory bowel disease (IBD) and aim to control the disease and improve quality of life. This study investigated changes in nonbiologic medication prescriptions for IBD patients initiating biologic therapy in Germany. Methods: This study used data from anonymized pharmacy records in the German longitudinal prescription (LRx) database and included biologic-naive IBD patients who received their first biologic therapy prescription between 2016 and 2022. Changes in prescription rates and pill counts for nonbiologic medications (corticosteroids, 5-aminosalicylates (5-ASA), proton pump inhibitors, analgesics, immunosuppressants, Vitamin D, iron, and antibiotics) before and after the initiation of biologic therapy were assessed using descriptive statistics, McNemar's tests, and Poisson regression models, adjusting for age and sex. Results: A total of 29,559 biologic-naive IBD patients were included. Prior to index, 91.2% received at least one nonbiologic medication prescription, where corticosteroids and 5-ASA were the most common. Postindex, the overall prescription rate decreased to 87.7%, with significant reductions in prescriptions observed for corticosteroids, 5-ASA, and immunosuppressants (p-values < 0.001). The mean (SD) pill count dropped from 704 (1712) to 514 (1651), with the largest mean differences (95% CI) having been for corticosteroids (−77.9 [−80.3 to −75.5]), 5-ASA (−61.6 [−65.2 to −58.1]), and immunosuppressants (−55.0 [−57.5 to −52.6]). Older patients tended to have greater decreases in pill counts for corticosteroids and 5-ASA, while males showed statistically significant reductions in pill count for immunosuppressants compared with females. Conclusions: This study demonstrates that the prescription of nonbiologic medications significantly decreased after biologic therapy initiation. The use of biologics may therefore lead to improved disease management and potentially better patient outcomes. [ABSTRACT FROM AUTHOR]

Colorectal cancer represents one of the most serious complications of inflammatory bowel disease. The NLRP3 inflammasome plays a pivotal role in the onset and progression of inflammatory bowel disease and is also implicated in colorectal cancer. This study aimed to investigate whether NLRP3 deficiency or glyburide, a sulfonylurea used for diabetes management and known as an NLRP3 inhibitor, could suppress colitis and its related colorectal tumorigenesis. Mice were divided into three groups: a control group, a glyburide group, and an NLRP3-deficient group. We investigated acute colitis and inflammation-related tumor models using azoxymethane and dextran sodium sulfate. In the colitis model, the colonic inflammation grade was significantly increased in NLRP3-deficient mice but not in mice administered glyburide. In the colorectal carcinogenesis model, fewer colorectal tumors were observed in both NLRP3-deficient and glyburide-treated groups. Additionally, a reduction in the expression levels of inflammatory cytokine genes was detected in the colonic mucosa of the mice of these groups. These findings suggest that NLRP3 deficiency may exacerbate acute colitis, while pharmacological inhibition, as well as deficiency of NLRP3, suppresses colitis-related tumorigenesis, presumably due to the attenuation of chronic inflammation in the colorectum. Glyburide holds promise as a potential chemopreventive agent for colitis-related colorectal cancer. [ABSTRACT FROM AUTHOR]