Course Of Ulcerative Colitis Research Articles

Circulating Extracellular Matrix Products as Indicators of Disease Burden and Predictors of Disease Course in Ulcerative Colitis.

Ulcerative colitis (UC) is characterized by recurrent inflammation and challenging disease monitoring, with invasive endoscopy as the primary diagnostic tool despite the inadequacy of standard noninvasive biomarkers. This study evaluates serum extracellular matrix (ECM) fragments, which reflect the remodeling of mucosa and submucosa, as potential indicators of disease burden and treatment efficacy. We aim to determine whether serum ECM levels correlate with the extent and severity and predict treatment response. We conducted a prospective study comparing serum ECM formation (PRO-C3, PRO-C7, PRO-C11, PRO-C22), turnover (PRO-C4), and degradation markers (C1M, C3M, C4M, C7M) at Weeks 0, 12, and 24 in 49 UC patients and 50 healthy controls measured by enzyme-linked immunosorbent assay. ECM biomarkers, notably PRO-C11, differentiated UC patients from controls (area under the curve [AUC] 0.77), and PRO-C3 predicted endoscopic treatment response vs nonresponse (AUC 0.74). C7M separated moderate from severe disease in endoscopy (AUC 0.74) as well as mild from severe disease (AUC 0.84), as did the ratio C7M/PRO-C7 (AUC 0.82). Combining new and conventional markers, including hemoglobin, C-reactive protein, PRO-C3, and PRO-C22, achieved a combined AUC of 0.84 for predicting 24-week endoscopic response, adding index endoscopic activity increased the AUC to 0.92 compared to an AUC of 0.84 for endoscopy alone. Soluble ECM fragments reflect endoscopic disease severity and extent and are also predictive of therapeutic efficacy. They may as well reflect degenerative aspects of UC and may as such be future therapeutic targets aimed at prevention of intestinal damage.

Impact of physical activity on gastrointestinal health and prevention and treatment of common gastrointestinal diseases: Irritable Bowel Syndrome and Inflammatory Bowel Diseases

Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Diseases (IBD), among them Crohn's disease and ulcerative colitis, are common chronic diseases affecting a growing group of patients. Physical activity (PA) is an important part of a healthy lifestyle. The aim of the study was to critically evaluate current knowledge of impact of PA on gastrointestinal (GI) health and prevention and treatment of some most common GI tract diseases, such as IBS and IBD. The comprehensive research of literature available on PubMed, Google Scholar, ResearchGate and Springer Link was performed. PA improves function of GI by increasing colon transit and bowel movements. These mechanisms contribute to reducing the risk of colorectal cancer and, to varying degrees depending on location, other digestive-system cancers. There is a potential association between PA and the more health-beneficial gut microbiota, but more research in this area is needed. Sedentary lifestyle seems to be a risk factor for IBD, while physical activity seems to be a protective factor only for Crohn disease. Altough, PA contributes to improvement of quality of life and reduction of stress in patients with IBD, futher conclusions on the effect of PA on the course of ulcerative colitis and Crohn disease still require expanded research. Available literature suggests that physical activity prevents obesity, a proven risk factor for worsening the course of the disease, and osteoporosis, an important complication of glucocorticosteroid therapy. Despite evidence of a sedentary lifestyle as a risk factor for IBS, there is still a lack of studies examining the impact of physical activity as a protective factor. the number of RCTs examining the effect of PA on the course of IBS remains insufficient, and studies conducted should take into account the various symptoms of IBS.

Protective role of TRPM7 knockdown in ulcerative colitis via blocking NLRP3 inflammasome-mediated pyroptosis

Transient receptor potential melastatin 7 (TRPM7) has been emerged as a potent drug target for immunomodulation with ion conductance and kinase activities. The research is projected to characterize the influences of TRPM7 on the course of ulcerative colitis (UC) and dissect the latent response mechanisms. The in vivo murine model and in vitro cell model of UC were both stimulated by DSS. RT-qPCR and western blotting tested the abundance of TRPM7. Colonic damage was estimated by Hematoxylin-eosin staining, calculation of colon length, measurement of DAI and MPO assay kit. CCK-8 method and TUNEL staining severally ascertained cell activity and apoptosis. ELISA method assayed the inflammatory levels and relevant assay kits determined oxidative stress levels. FITC-dextran flux, immunohistochemistry, TEER as well as western blotting evaluated intestinal barrier function. Immunofluorescence staining and western blotting appraised NLR family pyrin domain containing 3 (NLRP3)-dependent pyroptosis. Depleted TRPM7 retarded inflammation, oxidative damage as well as intestinal barrier damage both in vitro and in vivo. TRPM7 reduction repressed the pyroptosis mediated by NLRP3 inflammasome. NLRP3 agonist nigericin partly abolished the protection elicited by TRPM7 silencing against inflammation, oxidative damage as well as intestinal barrier damage in vitro. Collectively, TRPM7 deletion might possess the therapeutic potential in UC, the working mechanism of which might involve the inactivation of NLRP3-dependent pyroptosis.

Evaluation of Salvia officinalis in the Treatment of Acetic Acid-Induced Ulcerative Colitis in a Rat Model

Abstract Introduction Ulcerative colitis (UC) is an inflammatory bowel disease that causes long-lasting inflammation and ulcers within the digestive tract. This study aims to determine the histochemical alteration of Salvia officinalis (sage), an anti-inflammatory and antioxidant herbal agent on UC. Materials and Methods The disease was induced in 37 Sprague-Dawley rats with 2 mL of 3% acetic-acid (AA) enema. The rats were divided into five groups: a control group (AA), two 5-aminosalicylic (5-ASA) groups treated either orally (AO) or rectally (AR) with a dose of 100 mg/kg, and two salvia groups treated with 300mg/kg salvia orally (SO) or rectally (SR). Histopathological analyses of the colon were done on day 7, and markers such as C-reactive protein (CRP), superoxide dismutase (SOD), and complete blood count were measured. Result In macroscopic evaluation, the AO group demonstrated the lowest involvement, followed by the SO, SR, AR, and AA groups, respectively (p = 0.01). There was no significant difference between the SO and AO groups (p = 0.10), and the SR and AR groups (p = 0.58). Regarding microscopic histopathological findings, the AO and SO group demonstrated the most satisfactory results, with no significant difference between the AO versus SO, and AR versus SR groups. Inflammation was resolved in all of the AO and SO subjects. Conclusion Salvia can be beneficial in the treatment course of UC by inhibiting inflammatory responses, increasing the growth and viability of intestinal mucosa, and its antioxidant effects. Therefore, we propose the prescription of salvia as an adds-on or alternative therapy in the management of UC.

Natural course of ulcerative colitis in China: Differences from the West?

Whether the natural course of ulcerative colitis (UC) in mainland China is similar or different from that in Western countries is unknown, and data on it is limited. We aimed to provide a comprehensive description of the natural course of UC in China and compare it with Western UC patients. Based on a prospective Chinese nationwide registry of consecutive patients with inflammatory bowel diseases, the medical treatments and natural history of UC were described in detail, including disease extension, surgery, and neoplasia. The Cox regression model was used to identify factors associated with poor outcomes. A total of 1081 UC patients were included with a median follow-up duration of 5.3years. The overall cumulative exposure was 99.1% to 5-aminosalicylic acids, 52.1% to corticosteroids, 25.6% to immunomodulators, and 15.4% to biologics. Disease extent at diagnosis was proctitis in 26.9%, left-sided colitis in 34.8%, and extensive colitis in 38.3%. Of 667 patients with proctitis and left-sided colitis, 380 (57.0%) experienced disease extent progression. A total of 58 (5.4%) UC patients underwent colectomy, demonstrating cumulative proportions of surgery at 1, 5, and 10years after diagnosis of 0.6%, 3.4%, and 8.2%, respectively. In addition, 23 (2.1%) UC patients were diagnosed with neoplasia, demonstrating cumulative proportions of neoplasia at 1, 5, and 10years after diagnosis of 0.5%, 1.0%, and 3.5%, respectively. Chinese UC patients had similar cumulative proportions of exposure to IBD-specific treatments but a lower surgical rate than patients in Western countries, indicating a different natural course, and close monitoring needs for UC in China. However, these results must be confirmed in population-based studies because the hospital-based cohort in our study might lead to selection bias.

Clinical course of ulcerative colitis: Frequent use of biologics and low colectomy rate first year after diagnosis-results from the IBSEN III inception cohort.

The introduction of biologic therapies and the 'treat-to-target' treatment strategy may have changed the disease course of ulcerative colitis (UC). To describe the early disease course and disease outcome at 1-year follow-up in a population-based inception cohort of adult patients with newly diagnosed UC. The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study with prospective follow-up. Patients newly diagnosed with inflammatory bowel disease during 2017-2019 were included. Patients ≥18 years at diagnosis of UC who attended the 1-year follow-up were investigated. We registered clinical, endoscopic and demographic data at diagnosis and 1-year follow-up. We included 877 patients with UC (median age 36 years (range: 18-84), 45.8% female). At diagnosis, 39.2% presented with proctitis, 24.7% left-sided colitis and 36.0% extensive colitis. At the 1-year follow-up, 13.9% experienced disease progression, and 14.5% had received one or more biologic therapies. The colectomy rate was 0.9%. Steroid-free clinical remission was observed in 76.6%, and steroid-free endoscopic remission in 68.7%. Anaemia and initiation of systemic steroid treatment at diagnosis were associated with biologic therapy within the first year after diagnosis. In this population-based inception cohort, colectomy rate in the first year after diagnosis was low, and a high proportion of patients were in remission at 1-year follow-up. The use of biologic therapy increases, consistent with findings from previous studies.

Endoscopic picture of pseudopolyposis in inflammatory bowel diseases

Aim. To evaluate the frequency of pseudopolypes (PP), as well as their histological structure in patients with inflammatory bowel diseases (IBD). Materials and methods. 165 patients with IBD were examined (113 with ulcerative colitis (UC), 52 with Crohn’s disease (CD)). All patients underwent ileocolonoscopy with taking the material for histological examination in case pseudopolypes were detected. Results. It was revealed that pseudopolypes were found in 27% of patients with IBD (in UC - in 29%, CD - 23%). In different phases of the inflammatory process in UC, the number of PP was comparable to each other. In CD, PP was statistically significantly more often detected at the stage of scars and outside of exacerbation than in the phases of infiltration and ulcers. During histological examination of biopsy material from PP tissue hyperplasia, inflammatory polyp and granulation tissue were verified. Adenoma was detected in one case in each of the IBD. Crypt abscesses and crypt discomplexation were found only with exacerbation of UC. Conclusion. Based on the results of our study, pseudopolypes occur in both UC and CD in different phases of the inflammatory process, which indicates the absence of specificity of these tumors for any of the IBD. The identification of a large number of PP at a pronounced stage of UC, in our opinion, indicates the connection of PP with an aggressive attack, which can serve as one of the criteria for predicting the course of UC. The cellular composition of PP in most cases reflected inflammation or healing of erosive and ulcerative defects, as well as in a small number of cases, the presence of adenoma. Thus, PP requires careful examination during endoscopic examination, if there is a suspicion of neoplasia or dysplasia in the PP tissue, biopsies must be taken for histological examination.

Influence of Vitamin D Receptor Signalling and Vitamin D on Colonic Epithelial Cell Fate Decisions in Ulcerative Colitis.

Epidemiological studies have shown that subnormal levels of vitamin D (25[OH]D) are associated with a more aggravated clinical course of ulcerative colitis [UC]. Despite an increased focus on the therapeutic importance of vitamin D and vitamin D receptor [VDR] signalling, the mechanisms underlying the effects of the vitamin D-VDR axis on UC remain elusive. Therefore, we aimed to investigate whether exposure to active vitamin D (1,25[OH]2D3/VDR) signalling in human organoids could influence the maintenance of the colonic epithelium. Intestinal VDR expression was studied by immunohistochemistry, RNA expression arrays, and single-cell RNA sequencing of colonic biopsy specimens obtained from patients with UC and healthy individuals. To characterise the functional and transcriptional effects of 1,25[OH]2D3, we used patient-derived colonic organoids. The dependency of VDR was assessed by knocking out the receptor with CRISPR/Cas9. Our results suggest that 1,25[OH]2D3/VDR stimulation supports differentiation of the colonic epithelium and that impaired 1,25[OH]2D3/VDR signalling thereby may compromise the structure of the intestinal epithelial barrier, leading to flares of UC. Furthermore, a transcriptional response to VDR activity was observed primarily in fully differentiated cells at the top of the colonic crypt, and this response was reduced during flares of UC. We identified an important role of vitamin D signalling in supporting differentiated cell states in the human colonic epithelium, and thereby maintenance of the intestinal barrier integrity. This makes the vitamin D-VDR signalling axis an interesting target for therapeutic efforts to achieve and maintain remission in patients with UC.

Clinical statistical analysis plan for the ACCURE trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicentre trial

BackgroundThe primary treatment of ulcerative colitis (UC) is medical therapy using a standard step-up approach. An appendectomy might modulate the clinical course of UC, decreasing the incidence of relapses and reducing need for medication. The objective of the ACCURE trial is to assess the efficacy of laparoscopic appendectomy in addition to standard medical treatment in maintaining remission in UC patients. This article presents the statistical analysis plan to evaluate the outcomes of the ACCURE trial.Design and methodsThe ACCURE trial was designed as a multicentre, randomised controlled trial. UC patients with a new diagnosis or a disease relapse within the past 12 months, treated with 5-ASA, corticosteroids, or immunomodulators until complete clinical and endoscopic remission (defined as total Mayo score < 3 with endoscopic subscore of 0 or 1), were counselled for inclusion. Also, patients previously treated with biologicals who had a washout period of at least 3 months were considered for inclusion. Patients were randomised (1:1) to laparoscopic appendectomy plus maintenance treatment or a control group (maintenance therapy only). The primary outcome is the 1-year UC relapse rate (defined as a total Mayo-score ≥ 5 with endoscopic subscore of 2 or 3, or clinically as an exacerbation of symptoms and rectal bleeding or FCP > 150 or intensified medical therapy other than 5-ASA therapy). Secondary outcomes include number of relapses per patient, time to first relapse, disease activity, number of colectomies, medication usage, and health-related quality of life.DiscussionThe ACCURE trial will provide comprehensive evidence whether adding an appendectomy to maintenance treatment is superior to maintenance treatment only in maintaining remission in UC patients.Trial registrationDutch Trial Register (NTR) NTR2883. Registered May 3, 2011. ISRCTN, ISRCTN60945764. Registered August 12, 2019.

Constituents of stable commensal microbiota imply diverse colonic epithelial cell reactivity in patients with ulcerative colitis

BackgroundDespite extensive research on microbiome alterations in ulcerative colitis (UC), the role of the constituent stable microbiota remains unclear.ResultsThis study, employing 16S rRNA-gene sequencing, uncovers a persistent microbial imbalance in both active and quiescent UC patients compared to healthy controls. Using co-occurrence and differential abundance analysis, the study highlights microbial constituents, featuring Phocaeicola, Collinsella, Roseburia, Holdemanella, and Bacteroides, that are not affected during the course of UC. Co-cultivation experiments, utilizing commensal Escherichia coli and Phocaeicola vulgatus, were conducted with intestinal epithelial organoids derived from active UC patients and controls. These experiments reveal a tendency for a differential response in tight junction formation and maintenance in colonic epithelial cells, without inducing pathogen recognition and stress responses, offering further insights into the roles of these microorganisms in UC pathogenesis. These experiments also uncover high variation in patients’ response to the same bacteria, which indicate the need for more comprehensive, stratified analyses with an expanded sample size.ConclusionThis study reveals that a substantial part of the gut microbiota remains stable throughout progression of UC. Functional experiments suggest that members of core microbiota – Escherichia coli and Phocaeicola vulgatus – potentially differentially regulate the expression of tight junction gene in the colonic epithelium of UC patients and healthy individuals.

DOP25 Antibodies against Neutrophil Extracellular Traps (ANETAs) are associated with more severe disease course in Ulcerative Colitis

Abstract Background Antibodies against Neutrophil Extracellular Traps (ANETAs) have emerged as markers in multiple autoimmune disorders (i.e. rheumatoid arthritis and systemic lupus) associated with disease activity. We investigated the presence of ANETAs and their influence on disease course in Inflammatory Bowel Disease (IBD). Methods Serum samples from UC (n=33), Crohn's Disease (CD; n=28), and healthy controls (HC; n=8) underwent incubation with non-lytic Neutrophil Extracellular Traps (NETs) for immunofluorescence microscopy. For clinical relevance, these patients were followed over ten years to track treatment resistance, extraintestinal manifestations, surgeries, and disease recurrence (Table 1). For functional relevance, in vitro generated NETs were exposed to ANETAs, followed by quantifying macrophage-mediated clearance of these ANETA pre-treated NETs by real-time microscopy via pHrodo for 24 hours, as well as assessing pro-inflammatory cytokine (IL-6, TNF-α, IL-8, and IL-23) genetic expression levels in these macrophages. Results Among UC patients, ANETA positivity correlated with high rates of treatment resistance, extraintestinal manifestations, colorectal surgeries, and recurrence of disease like pouchitis (93.3% vs. 6.7%, 61.5% vs. 38.5%; 71.4% vs. 28.6%; 87.5% vs. 12.5%, for ANETA+ and ANETA- UC patients, respectively). CD patients with ANETAs exhibited high rates of resistance to treatment (75% vs 25%) and lower rates of extraintestinal manifestations, colectomy, and disease recurrence (38.1% vs 61.9%, 40% vs 60%, 33.3% vs 66.7%) (Fig 1A). Macrophages displayed robust engulfment of untreated NETs and those treated with healthy control sera, while ANETA-coated NETs exhibited reduced susceptibility to macrophage phagocytosis (Fig 1B). Gene expression analysis revealed a significant upregulation of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-23) when NETs were incubated with serum from ANETA-positive individuals compared to sera from healthy controls (p&amp;lt;0.05). Conclusion ANETAs may serve as markers for a distinct subgroup of UC patients characterized by aggressive disease and poorer prognosis. The potential mechanism might involve impaired NETs clearance by, and inducing a proinflammatory response in macrophages. Discrepancies observed between UC and CD suggest diverse pathophysiological mechanisms in both diseases. Further research is imperative to comprehensively understand the underlying pathophysiology, function, and potential clinical applications of ANETAs in IBD.

P472 A Real World Practice of Intestinal Ultrasound in the Monitoring of Disease Activity in Ulcerative Colitis

Abstract Background Intestinal ultrasound (IUS) has emerged as an important monitoring tool in the clinical course of ulcerative colitis (UC). Previously known factors about UC have been considered in terms of the associations with IUS. However, a few studies reported about the associations between the findings of IUS and clinical factors. Methods We performed a multi-center, cross-sectional study of patients with UC who received IUS and clinical exams including endoscopy simultaneously. The primary endpoint was the association between endoscopic disease activity as Mayo endoscopic score (MES) and IUS finding as Milan ultrasound criteria (MUC). The secondary endpoint comprised the various clinical factors associated with MUC. Patients with MUC&amp;lt;6.2 were defined as low MUC group and others as high MUC group. Results A total of 35 patients were enrolled in this study. The numbers of Low- and high-MUC groups were 23 and 12, respectively. The median age in each group was 41 and 53 years old. The portion of male sex in each group was 57% and 75%. There were no significant differences in terms of body mass index, onset age, disease duration, current medication such as 5-aminosalicylic acid, steroid, immunomodulator, and biologics and small molecules between both groups. Compared with low and high MUC groups, endoscopic remission was more significantly associated with the low MUC group than the high MUC group (35% vs. 0, p = 0.032). In addition, the rate of disease activity ranged from remission to mild, as tolerable clinical activity, was also significantly higher in the low MUC group than the high MUC group (91% vs. 58%, p = 0.033). Other outcomes such as symptomatic remission, histologic remission, and biochemical response revealed similar rates between the two groups. Conclusion Low MUC of IUS in the patients with UC showed significant clinical association such as endoscopic remission and tolerable clinical activity. This study is now ongoing prospective research and further investigation into the relationship between IUS and clinical outcomes of UC will elicit robust results.

P972 Short and long-term outcomes after acute severe ulcerative colitis in children: A Canadian single centre experience

Abstract Background The short and long-term course of ulcerative colitis (UC) following an episode of acute severe UC (ASUC) in children is insufficiently characterized. We aimed to assess contemporary outcomes in children hospitalized with ASUC. Methods This was a retrospective cohort study of children aged 2-17 years hospitalized with ASUC between 2010 and 2022 at a tertiary center in London, Ontario, Canada. All data were recorded using standardised Case Report Forms, de-identified, and entered into a central database registry using Research Electronic Data Capture (REDCap) Steroid non-response was defined as requirement of medical rescue therapy or colectomy. Results A total of 58 children hospitalized with ASUC were included (male: 55.2% [n =32], mean age at admission: 12.2 ± 3.5 years). The majority had extensive colitis (82.4% [n = 42]) at the time of diagnosis. 74% (n = 43) presented within one year of symptom onset and 31% (n = 18) had ASUC as their index presentation with UC. 15.5% (n = 9) of patients had prior purine analogues and 20.7% (n = 12) had received biologics prior to ASUC presentation. Median Pediatric Ulcerative Colitis Activity Index (PUCAI) score on admission was 65.0 (IQR: 60.0 – 75.0). After intravenous corticosteroid therapy 68.9% (n = 40) responded to steroids. Of the patients with steroid non-response (31% [n = 18]), 3.4% (2/58) underwent colectomy and 27.6% (16/58) patients received infliximab rescue therapy. Median PUCAI score was significantly lower on day 3 between steroid responders and steroid non-responders (37.5 vs 60, p &amp;lt;0.01). The short term (3 months following discharge) and long-term (3-12 months following discharge) colectomy rates following discharge were 7.4% (4/54) and 8% (4/50) respectively. Short term and long-term hospitalization rates for UC exacerbation following discharge was 25.9% (14/54) and 16% (8/50) respectively. Similar rates of long-term colectomy and hospitalizations were observed between steroid responders and non-responders. On univariate analysis, no statistically significant factors associated with steroid non-response were identified. Conclusion 17% of patients hospitalized for ASUC required colectomy within 12 months of presentation. Despite a high initial response to corticosteroids, long term colectomy rates and re-hospitalization rates are still high. Future research should focus on earlier identification and treatment of children at high risk of exacerbation to prevent complications.

P955 The effect of appendicectomy on the clinical course of Ulcerative Colitis: Preliminary results

Abstract Background Emerging evidence indicates an immunomodulatory role of the appendix in ulcerative colitis (UC). Previous studies have suggested a beneficial effect of appendicectomy in inducing and maintaining remission. Therefore, appendicectomy may be considered as an alternative or adjunctive treatment in UC. Aim To evaluate the efficacy of appendicectomy in maintaining remission in UC patients. Methods Adult patients with established UC in complete clinical and endoscopic remission (defined as Mayo score &amp;lt;3 with endoscopic subscore of 0 or 1) following medical induction treatment for disease relapse within 12 months prior to randomisation, were enrolled in the Netherlands and United Kingdom. Patients were randomised (1:1) to undergo appendicectomy (intervention group) or continue maintenance medical therapy (control group). The primary outcome was the one-year UC relapse rate (defined as a total Mayo-score score ≥5 with endoscopic subscore of ≥2). To detect a clinically relevant decrease in relapse rate from 40% to 20%, 82 patients per study arm were needed to achieve 80% power. The last patient was included in September 2022, so analysis of the primary outcome parameter is expected to start soon. Trial progress, including the accumulated number of (serious) adverse events (SAE) in both groups, were presented annually to the Data Safety Monitoring Board. Therefore safety data is available. Results In total, 99 patients were included in the intervention group and 99 patients in the control group. There were 86 males and 112 females, with a median age of 41 years (IQR 33-52). Baseline characteristics were comparable in both groups, with the majority of patients having proctitis (38.9%) or left sided colitis (35.9%). Three SAEs were reported in the appendicectomy group, 2 of which were related to the surgical procedure (reintervention for obstructive ileus and postoperative hematoma) and one hospitalisation for clostridium infection. One SAE was reported within the first year in the control group (appendicitis). The one-year reported colitis-associated adverse event rate was significantly lower in the appendicectomy group when compared to the control group (46.4% vs. 63.9%, P=0.02). During follow up there were no colectomies in the appendicectomy group, whereas three patients underwent colectomy for therapy-refractory disease in the control group. Conclusion Appendicectomy in patients with UC has the possibility to decrease the rate of colitis-associated (serious) adverse events. These results suggest that the final analysis of the primary outcome parameter (relapse rate) could demonstrate that appendicectomy is superior to standard medical therapy alone in maintaining remission in these patients.

P471 Tight control strategy improves combined histologic and endoscopic remission in ulcerative colitis

Abstract Background Increasing evidence suggests that combined histological and endoscopic remission associates with less adverse outcomes (hospitalization and corticosteroid therapy) and predicts a quiescent course of ulcerative colitis (UC). However, few patients can achieve this target with the drugs currently available. A tight control strategy with a proactive treatment escalation based on biomarkers may improve these results. Methods Retrospective, single-center cohort study including consecutive patients with UC with severe endoscopic disease (Mayo endoscopic subscore=3) and subsequent endoscopic, histologic and faecal calprotectin (FCP) evaluation. Data concerning demographic, disease phenotype, laboratory findings and treatment were collected. We defined tight control strategy as therapeutic escalation in &amp;gt;50% of cases where FCP≥250ug/g. Therapeutic escalation was defined as the start, switch or dose increment/interval shortening of biologic therapies/small molecules. Endoscopic remission was defined as a Mayo endoscopic subscore ≤1. Histologic remission was defined as the absence of ulcers, erosions and neutrophils in the lamina propria. Results One hundred and seven patients were included, 56.0% male and 63.6% with extensive UC. Thirty-four patients (31.8%) were included in the tight control group. During follow up, 52 patients (48.6%) achieved endoscopic remission, 29 (27.1%) histological remission and 27 (25.1%) combined remission. Patients in the tight control group achieved combined remission more frequently (38.2 vs 19.2%, P=0.05). On multivariate analysis including age at diagnosis, duration and extension of disease and therapy received, a tight control strategy was independently related to a higher probability of combined remission: OR 2.768 IC95% 1.056-7.255, P=0.038. Conclusion A tight control strategy based on FCP was associated with higher combined histological and endoscopic remission in UC.

P219 Prognostic potential of mucosal proteins in Ulcerative Colitis

Abstract Background Better prognostic measures for ulcerative colitis (UC) could significantly advance patient care. While the prognostic capacity of circulating proteins in UC has been explored, the role of mucosal proteins remains largely unknown. We examined mucosal protein markers in patients with incident ulcerative colitis and evaluated their prognostic value. Methods Biopsies from macroscopically inflamed colonic/rectal mucosa of adult patients in the Swedish inception cohort of IBD (SIC IBD) were obtained at diagnosis of UC. Patients were followed prospectively, and clinical data were recorded after 3 and 12 months. Disease course was categorised as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents; the use of &amp;gt;2 courses of corticosteroids, or a cumulative dose of &amp;gt;2.5 g. Relative estimates of 162 protein markers were assessed in homogenised tissue supernatants, using proximity extension assay technology (Olink Proteomics, Uppsala, Inflammation and Oncology II panel). Mann-Whitney U test, with Benjamini-Hochberg correction was used to identify differentially regulated mucosal proteins in aggressive vs indolent disease course, with a 5% false discovery rate (FDR). Smoothly clipped absolute deviation regularised logistic regression models were used to identify prognostic signatures distinguishing aggressive from indolent disease course. Performance was estimated in a leave-one-out cross-validation and reported as the area under the receiver operating characteristic (ROC) curve (AUC). Results 117 patients provided a macroscopically inflamed colonic/rectal biopsy at diagnosis of UC. Basic demographics and clinical characteristics are presented in Table 1. Relative protein levels of WFdc2 and CCL20 were significantly lower in lysates from patients developing an aggressive course vs patients developing an indolent course, while estimates of MMP1, CCL11, WISP-1, OPG, RSPO3 and VEGFR2 were higher (Figure 1A). Regularized logistic regression identified signatures restricted to 28 proteins, distinguishing aggressive from indolent UC courses, yielding an AUC of 0.68 (95% confidence interval (CI): 0.56-0.80) for left-out samples (Figure 1B). Incorporating extent of inflammation at diagnosis in the model improved the AUC to 0.71 (95% CI: 0.60-0.83). Conclusion We identified prognostic mucosal protein signatures associated with future course of ulcerative colitis by analysing inflamed mucosal biopsies that were obtained at diagnosis. These protein markers may highlight pathways of relevance for ulcerative colitis outcomes.

ECCO Grant Untangling the gut phagosome dynamics of the relapse/remission cycle in ulcerative colitis

Abstract Background and Aims The course of ulcerative colitis (UC) is usually characterized by intertwining periods of remission and relapse. Most microbiome UC studies focus on the gut bacteriome. However, recent studies on animal models suggest that phage-mediated bacterial cell lysis may play a role in sustaining gut inflammation, proving the phageome (collection of bacteriophages) should not be ignored in this disease. Therefore, this project aims to: 1) characterize the gut phageome of patients with UC who suffer from frequent relapses, 2) compare temporal dynamics of gut the phageome between patients and healthy controls, 3) To model interactions between bacteriome, mycobiome, phageome on one hand, and lifestyle factors (diet, stress levels, medication) on the other 4) To infer host status (relapse versus remission of the disease) based on phageome composition, and using interactions inferred in Objective 3. Methods The cohort comprises 24 patients with UC (14 of whom suffered from relapse) and 10 healthy controls, with stool samples collected monthly for a year. Phageome profiling will be achieved via shotgun sequencing of phage genomes from the same stool samples. This dataset will be interrogated together with bacterial (16S rRNA) and fungal (ITS) amplicon data, which have just been generated. Available metadata include disease symptoms, diet, stress levels, work productivity, medication, and faecal calprotectin. Dynamic time-wrapping algorithms will be used to align time series of microbial members with similar temporal dynamics. Dynamic Bayesian Network modelling will infer interactions between microbiome members and predict future relapse. Anticipated Impact The phageome is the often neglected (“dark matter”) part of the microbiome, but has defining interactions with bacteria. We will expand knowledge on inter-species dynamics during relapse and remission cycles of UC. This will potentially lead to new microbiome-related relapse predictors, which may contribute to new prognostic tools in UC, and potentially inform therapeutic avenues.

Clinical and epidemiological features of ulcerative colitis in children of the Rostov region

Russian data on the prevalence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC), confirm the general global trend towards an increase in IBD, taking into account age-related as well as regional characteristics, which determined the purpose of this study. The purpose of the study. To evaluate the clinical and epidemiological features of the course of ulcerative colitis in children of Rostov-on-Don. Materials and methods. We observed 42 children aged from 1 to 14 years with a diagnosis of UC, which was made on the basis of anamnesis, clinical picture, laboratory test results, colonoscopy data, and morphological examination of the colon mucosa. UC activity was assessed taking into account the PUCAI index. Results. For the period from 2014 to 2023 On the basis of the pediatric somatic department of city hospital No. 20 in Rostov-on-Don, UC was diagnosed in 42 children aged 1 to 14 years, which amounted to 1.48% of the total number of patients with chronic intestinal diseases (2822 people). There was an increase in the incidence of ulcerative colitis from 2014 to 2023 (from 0.32% to 2.52%) with maximum values in 2021-2023. Conclusion. Clinical and epidemiological studies have shown an increase in the incidence of UC in children of Rostov-on-Don over the past 10 years. It has been established that ulcerative colitis is more often detected in the preschool group of children. The incidence of ulcerative colitis was higher in boys than in girls. A high degree of family history of children with UC was revealed for diseases of the digestive system, delivery by Caesarean section, artificial feeding in the first year of life, and acute intestinal infections. In the UC clinic, milder, erased forms of the disease dominated, which determined the later diagnosis of the disease at the prehospital stage.

Linking microbial genes to plasma and stool metabolites uncovers host-microbial interactions underlying ulcerative colitis disease course

Understanding the role of the microbiome in inflammatory diseases requires the identification of microbial effector molecules. We established an approach to link disease-associated microbes to microbial metabolites by integrating paired metagenomics, stool and plasma metabolomics, and culturomics. We identified host-microbial interactions correlated with disease activity, inflammation, and the clinical course of ulcerative colitis (UC) in the Predicting Response to Standardized Colitis Therapy (PROTECT) pediatric inception cohort. In severe disease, metabolite changes included increased dipeptides and tauro-conjugated bile acids (BAs) and decreased amino-acid-conjugated BAs in stool, whereas in plasma polyamines (N-acetylputrescine and N1-acetylspermidine) increased. Using patient samples and Veillonella parvula as a model, we uncovered nitrate- and lactate-dependent metabolic pathways, experimentally linking V.parvula expansion to immunomodulatory tryptophan metabolite production. Additionally, V.parvula metabolizes immunosuppressive thiopurine drugs through xdhA xanthine dehydrogenase, potentially impairing the therapeutic response. Our findings demonstrate that the microbiome contributes to disease-associated metabolite changes, underscoring the importance of these interactions in disease pathology and treatment.

AI and endoscopy/histology in UC: the rise of machine.

The gap between endoscopy and histology is getting closer with the introduction of sophisticated endoscopic technologies. Furthermore, unprecedented advances in artificial intelligence (AI) have enabled objective assessment of endoscopy and digital pathology, providing accurate, consistent, and reproducible evaluations of endoscopic appearance and histologic activity. These advancements result in improved disease management by predicting treatment response and long-term outcomes. AI will also support endoscopy in raising the standard of clinical trial study design by facilitating patient recruitment and improving the validity of endoscopic readings and endoscopy quality, thus overcoming the subjective variability in scoring. Accordingly, AI will be an ideal adjunct tool for enhancing, complementing, and improving our understanding of ulcerative colitis course. This review explores promising AI applications enabled by endoscopy and histology techniques. We further discuss future directions, envisioning a bright future where AI technology extends the frontiers beyond human limits and boundaries.