Forms Of Inflammatory Bowel Disease Research Articles

A Comparison of Clinical Outcomes of Colectomies for Pediatric and Adult Patients With Inflammatory Bowel Disease.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are prevalent in adult and pediatric populations, but their differences are not well studied using national data. We compared the clinical outcomes of these patients using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) databases.Methods: Colectomy cases for CD and UC, the 2 major forms of inflammatory bowel disease (IBD), were compared between adult and pediatric patients using the 2017-2019 ACS NSQIP databases. Various clinical factors were analyzed, with postoperative complications being the primary outcome of interest.Results: We identified 542 pediatric and 5174 adult CD patients and 360 pediatric and 1292 adult UC patients. Adults with CD or UC were more likely to be on steroids preoperatively (CD: 60.15% vs 24.54%; UC: 65.63% vs 51.39%). Children with IBD were more likely to have preoperative transfusions (CD: 1.48% vs .33%; UC: 8.33% vs .62%), systemic inflammatory response syndrome (CD: 3.51% vs .93%; UC: 12.78% vs 3.10%), or sepsis (CD: 1.85% vs .66%; UC: 1.39% vs .31%). Unplanned reoperations were more common among pediatric patients in both disease states compared to adults (CD: 6.27% vs 4.10%; UC: 11.11% vs 4.26%), with P-values for all factors described as ≤.02. Multivariate logistic regression found pediatric age to be associated with higher odds of needing a reoperation among UC patients but not CD patients.Conclusion: Pediatric patients were sicker at the time of surgery, and those with either disease were more likely to require a reoperation within 30days.

Stromal-like Cells Are Found in Peripheral Blood of Inflammatory Bowel Disease Patients and Correlate with Immune Activation State.

Recent studies have identified a critical role for stromal-immune cell interactions in immunity and immune tolerance. Transcriptomic profiling has implicated stromal cells in immune-mediated disorders including the two common forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). Stromal-immune interactions may edify inflammatory state and the development of IBD-related complications such as fibrosis; yet the lack of protein markers has hampered studying stromal-immune perturbation. In this study, we designed a 40-color spectral flow cytometry assay to characterize hematopoietic and nonhematopoietic cells in intestinal biopsies and matched blood samples from patients with CD or UC. We identified circulating stromal-like cells that are significantly more abundant in IBD blood samples than in healthy controls. Those cells expressed podoplanin (PDPN), a commonly used marker for fibroblasts, and they were associated with activated and memory T and B cells, and altered NK cell, monocyte, and macrophage populations. PDPN+ cells in the blood correlated with PDPN+ cells in the colon. Principal component analysis distinctly separated healthy blood samples from IBD blood samples, with stromal-like cells and B cell subtypes dominating the IBD signature; Pearson correlation detected an association between PDPN+ stromal-like cells and B cell populations in IBD blood and gut biopsies. These observations suggest that PDPN+ cells in the blood may serve as a biomarker of IBD. Understanding the relationship between stromal cells and immune cells in the intestine and the blood may provide a window into disease pathogenesis and insight into therapeutic targets for IBD.

Association between inflammatory bowel disease and primary sclerosing cholangitis: Insights from bibliometric analysis.

Crohn's disease and ulcerative colitis are forms of inflammatory bowel disease affecting approximately 1% of the population. Their typical features include chronic diarrhea, abdominal pain, and weight loss. Extraintestinal manifestations may coincide with or precede the diagnosis of these diseases. Primary sclerosing cholangitis is one such extraintestinal manifestation. Although many papers on this field have been published, bibliometric analysis still needs to be conducted. This article summarizes the current research progress through a bibliometric study, provides an overview of the research status in this field, and analyzes recent research trends. Publications on inflammatory bowel disease and primary sclerosing cholangitis from January 1, 2008, to August 31, 2023, were extracted from the Web of Science Core Collection. VOSviewer and CiteSpace were used to perform a bibliometric and visual study. There are 1499 relevant articles, and the number of articles in this field has been relatively stable in recent years. The results indicate that Karlson TH from the University of Oslo has the highest cumulative number of publications. The institution with the highest publication output is the Mayo Clinic, and the United States leads in article production, occupying a dominant position. Keyword analysis reveals 4079 keywords, with primary sclerosing cholangitis, inflammatory bowel disease, and ulcerative colitis being the most frequently occurring keywords. Research on the association between inflammatory bowel disease and primary sclerosing cholangitis is steadily advancing, with the United States leading in publication output globally. China needs to invest more in research in this area, and collaboration among institutions should be strengthened. The research hotspots revolve around the association between inflammatory bowel disease and primary sclerosing cholangitis, gut microbiota, and other fields.

Serum Leucine-Rich α2 Glycoprotein Could Be a Useful Biomarker to Differentiate Patients with Normal Colonic Mucosa from Those with Inflammatory Bowel Disease or Other Forms of Colitis.

(1) Background: Serum leucine-rich α2 glycoprotein (LRG) has been reported as a useful biomarker for monitoring disease activity in patients with inflammatory bowel disease (IBD). We investigated whether serum LRG can differentiate patients with normal colonic mucosa from those with IBD or other forms of colitis. (2) Methods: Patients with diarrhea, abdominal pain, or bloody stools were consecutively enrolled at their initial visit to our hospital. Serum LRG and C-reactive protein were measured, and a colonoscopy and histology were performed. (3) Results: We enrolled 317 patients (181 men, 136 women; median age: 51 years). Based on the endoscopic and histological criteria, 260 patients were diagnosed with ulcerative colitis (n = 134), Crohn's disease (n = 10), infectious colitis (n = 43), diverticular colitis (n = 17), or nonspecific colitis (n = 56). The remaining 57 patients were diagnosed with normal colonic mucosa including histology. The latter group's median LRG value (9.5 µg/mL, range: 5.8-13.5) was significantly lower than that of the other 260 patients (13.6 µg/mL, range: 6.8-62.7, p < 0.0001). The optimal LRG cut-off value of <10.4 µg/mL was derived from the receiver operating characteristic (ROC) curve, showing a 91% sensitivity and 77% specificity for identifying patients with normal colonic mucosa. (4) Conclusions: serum LRG values < 10.4 µg/mL could be a useful biomarker for predicting patients with normal colonic mucosa.

Moringin alleviates DSS-induced ulcerative colitis in mice by regulating Nrf2/NF-κB pathway and PI3K/AKT/mTOR pathway

Ulcerative colitis (UC) is a main form of inflammatory bowel disease (IBD), which is a chronic and immune-mediated inflammatory disease. Moringin (MOR) is an isothiocyanate isolated from Moringa oleifera Lam., and has been recognized as a promising potent drug for inflammatory diseases and antibacterial infections. The present study investigated the role of moringin in dextran sulfate sodium (DSS)-induced UC mice. Mouse colitis was induced by adding DSS to the drinking water for seven consecutive days. Our experimental results showed that MOR relieves DSS-induced UC in mice by increasing body weight and colonic length, and reducing the disease activity index and histological injury. Mechanistically, MOR improves intestinal barrier function by increasing the expression of tight junction proteins (TJPs) and enhancing the secretion of mucin in DSS-induced mice. MOR inhibits inflammatory response and intestinal damage by regulating Nrf2/NF-κB signaling pathway and modulating the PI3K/AKT/mTOR pathway. Furthermore, in Nrf2 knockout (Nrf2-/-) mice, the protective effects of MOR on DSS-induced UC were abolished. Meanwhile, treatment with MOR reduced inflammation and cell damage via regulating Nrf2/NF-κB pathway in a lipopolysaccharide (LPS)-induced inflammation model of Caco-2 cells. In contrast, ML385, an Nrf2 inhibitor, might eliminate the protection provided by MOR. Notably, treatment with MOR significantly up-regulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), suggesting that MOR may be a potential PPAR-γ activator. In conclusion, MOR exerts protective effect in UC by improving intestinal barrier function, regulating Nrf2/NF-κB and PI3K/AKT/mTOR signaling pathways, and another effect associated with the regulation of PPAR-γ expression.

Effects of DNA methylation and its application in inflammatory bowel disease (Review).

Inflammatory bowel disease (IBD) is marked by persistent inflammation, and its development and progression are linked to environmental, genetic, immune system and gut microbial factors. DNA methylation (DNAm), as one of the protein modifications, is a crucial epigenetic process used by cells to control gene transcription. DNAm is one of the most common areas that has drawn increasing attention recently, with studies revealing that the interleukin (IL)‑23/IL‑12, wingless‑related integration site, IL‑6‑associated signal transducer and activator of transcription 3, suppressor of cytokine signaling 3 and apoptosis signaling pathways are involved in DNAm and in the pathogenesis of IBD. It has emerged that DNAm‑associated genes are involved in perpetuating the persistent inflammation that characterizes a number of diseases, including IBD, providing a novel therapeutic strategy for exploring their treatment. The present review discusses DNAm‑associated genes in the pathogenesis of IBD and summarizes their application as possible diagnostic, prognostic and therapeutic biomarkers in IBD. This may provide a reference for the particular form of IBD and its related methylation genes, aiding in clinical decision‑making and encouraging therapeutic alternatives.

Integrative analysis with microbial modelling and machine learning uncovers potential alleviators for ulcerative colitis

ABSTRACT Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of Parabacteroides merdae ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.

Oroxyloside protects against dextran sulfate sodium-induced colitis by inhibiting ER stress via PPARγ activation

Ulcerative colitis (UC), a prevalent form of inflammatory bowel disease (IBD), may result from immune system dysfunction, leading to the sustained overproduction of reactive oxygen species (ROS) and subsequent cellular oxidative stress damage. Recent studies have identified both peroxisome proliferator-activated receptor-γ (PPARγ) and endoplasmic reticulum (ER) stress as critical targets for the treatment of IBD. Oroxyloside (C22H20O11), derived from the root of Scutellariabaicalensis Georgi, has traditionally been used in treating inflammatory diseases. In this study, we investigated the molecular mechanisms by which oroxyloside mitigates dextran sulfate sodium (DSS)-induced colitis. We examined the effects of oroxyloside on ROS-mediated ER stress in colitis, including the protein expressions of GRP78, p-PERK, p-eIF2α, ATF4, and CHOP, which are associated with ER stress. The beneficial impact of oroxyloside was reversed by the PPARγ antagonist GW9662 (1 mg·kg-1, i.v.) in vivo. Furthermore, oroxyloside decreased pro-inflammatory cytokines and ROS production in both bone marrow-derived macrophages (BMDM) and the mouse macrophage cell line RAW 264.7. However, PPARγ siRNA transfection blocked the anti-inflammatory effect of oroxyloside and even abolished ROS generation and ER stress activation inhibited by oroxyloside in vitro. In conclusion, our study demonstrates that oroxyloside ameliorates DSS-induced colitis by inhibiting ER stress via PPARγ activation, suggesting that oroxyloside might be a promising effective agent for IBD.

Protective effect of synbiotic combination of Lactobacillus plantarum SC-5 and olive oil extract tyrosol in a murine model of ulcerative colitis

BackgroundUlcerative colitisis (UC) classified as a form of inflammatory bowel diseases (IBD) characterized by chronic, nonspecific, and recurrent symptoms with a poor prognosis. Common clinical manifestations of UC include diarrhea, fecal bleeding, and abdominal pain. Even though anti-inflammatory drugs can help alleviate symptoms of IBD, their long-term use is limited due to potential side effects. Therefore, alternative approaches for the treatment and prevention of inflammation in UC are crucial.MethodsThis study investigated the synergistic mechanism of Lactobacillus plantarum SC-5 (SC-5) and tyrosol (TY) combination (TS) in murine colitis, specifically exploring their regulatory activity on the dextran sulfate sodium (DSS)-induced inflammatory pathways (NF-κB and MAPK) and key molecular targets (tight junction protein). The effectiveness of 1 week of treatment with SC-5, TY, or TS was evaluated in a DSS-induced colitis mice model by assessing colitis morbidity and colonic mucosal injury (n = 9). To validate these findings, fecal microbiota transplantation (FMT) was performed by inoculating DSS-treated mice with the microbiota of TS-administered mice (n = 9).ResultsThe results demonstrated that all three treatments effectively reduced colitis morbidity and protected against DSS-induced UC. The combination treatment, TS, exhibited inhibitory effects on the DSS-induced activation of mitogen-activated protein kinase (MAPK) and negatively regulated NF-κB. Furthermore, TS maintained the integrity of the tight junction (TJ) structure by regulating the expression of zona-occludin-1 (ZO-1), Occludin, and Claudin-3 (p < 0.05). Analysis of the intestinal microbiota revealed significant differences, including a decrease in Proteus and an increase in Lactobacillus, Bifidobacterium, and Akkermansia, which supported the protective effect of TS (p < 0.05). An increase in the number of Aspergillus bacteria can cause inflammation in the intestines and lead to the formation of ulcers. Bifidobacterium and Lactobacillus can regulate the micro-ecological balance of the intestinal tract, replenish normal physiological bacteria and inhibit harmful intestinal bacteria, which can alleviate the symptoms of UC. The relative abundance of Akkermansia has been shown to be negatively associated with IBD. The FMT group exhibited alleviated colitis, excellent anti-inflammatory effects, improved colonic barrier integrity, and enrichment of bacteria such as Akkermansia (p < 0.05). These results further supported the gut microbiota-dependent mechanism of TS in ameliorating colonic inflammation.ConclusionIn conclusion, the TS demonstrated a remission of colitis and amelioration of colonic inflammation in a gut microbiota-dependent manner. The findings suggest that TS could be a potential natural medicine for the protection of UC health. The above results suggest that TS can be used as a potential therapeutic agent for the clinical regulation of UC.

MANAGEMENT OF GRAHANI ROGA WITH SPECIAL REFERENCE TO ULCERATIVE COLITIS: A CASE REPORT

Grahani roga is a disease of significant clinical relevance in the modern era. It is a disease caused by a faulty lifestyle, which includes defective dietary habits, regimen and psychological factors. It resembles the symptoms of Ulcerative colitis. It is a form of inflammatory bowel disease that causes inflammation and ulcers in the lining of the large intestine, especially in the rectum. Aims and objectives: To evaluate the effect of Piccha Basti along with Shirodhara in Grahani roga. Materials and methods: Takra Basti and Piccha Basti followed by Anuvasana Basti with Changeryadi ghrita in Kala Basti pattern, Shiro dhara with Medha kwatha ksheerapaka and shamana oushadhis were administered. Result: The treatment adopted is effective in the management of Grahani and has shown significant changes in the signs and symptoms of Grahani roga. Discussion: Takra Basti and Piccha Basti reduce the inflammation by its grahi, deepana and picchila guna. It also improves the functioning of Grahani. Piccha basti, due to its picchila guna, forms the coating over the intestine, thereby preventing further mucosa damage. Conclusion: Shodhana, shamana yoga, and dietic modification give maximum benefits. Hence, an effort has been made to treat Ulcerative colitis through Panchakarma.

New strategies in the diagnosis and treatment of immune-checkpoint inhibitor-mediated colitis.

Immune-checkpoint inhibitor-mediated colitis (IMC) is an increasingly recognized adverse event in cancer immunotherapy, particularly associated with immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte antigen-4 and anti-programmed cell death protein-1 antibodies. As this revolutionary immunotherapy gains prominence in cancer treatment, understanding, diagnosing, and effectively managing IMC becomes paramount. IMC represents a unique challenge due to its immune-mediated nature and potential for severe complications. However, a precise picture of IMC pathophysiology is currently unavailable. Therefore, we aimed to summarize the existing data while acknowledging the need for further research. This comprehensive review explores the mechanisms underlying ICIs, gastrointestinal adverse effects, and, in particular, IMC's incidence, prevalence, and features. Our review also emphasizes the importance of recognizing IMC's distinct clinical and histopathological features to differentiate it from other forms of colitis. Furthermore, this paper highlights the urgent need for evolving diagnostic methods, therapeutic strategies, and a multidisciplinary approach to effectively manage IMC.

MicroRNA-mRNA Networks Linked to Inflammation and Immune System Regulation in Inflammatory Bowel Disease.

By performing a comprehensive meta-analysis, we integrated miRNA expression data from nine studies in IBD. We obtained detailed information on significantly deregulated miRNAs (fold change, FC ≥ 2 and p < 0.05), sample type and number, and platform applied for analysis in the training and validation sets. Further bioinformatic analyses were performed to identify miRNA target genes, by using the microRNA Data Integration Portal tool. We also sought to identify statistically enriched pathways of genes regulated by miRNAs using ToppGene Suite. Additional analyses were performed to filter for genes expressed in intestinal tissue using the European Bioinformatics Institute (EBI) database. Our findings showed the upregulation of 15 miRNAs in CD and 33 in UC. Conversely, six miRNAs were downregulated in CD, while seven were downregulated in UC. These results indicate a greater deregulation of miRNAs in UC compared to CD. Of note, miRNA target genes were enriched for immune system regulation pathways. Among significantly deregulated miRNAs with a higher number of miRNA-target gene interactions, we identified miR-199a-5p and miR-362-3p altered in CD, while among UC case patients, miRNA-target gene interactions were higher for miR-155-5p. The identified miRNAs play roles in regulating genes associated with immune system regulation and inflammation in IBD. Such miRNAs and their target genes have the potential to serve as clinically relevant biomarkers. These findings hold promise for enhancing the accuracy of diagnoses and facilitating the development of personalized treatment strategies for individuals with various forms of IBD.

Association between serum omentin-1 and mucosal disease activity in patients with ulcerative colitis.

Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC. A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity. Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5-72.6 versus healthy controls, 103.5 interquartile range: 48.3-156.2ng/ml; P < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC. These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC.

UNIQUE MONOCYTE EXPRESSION SIGNATURE IN A STXBP2 MUTATION CAUSING INFANTILE ONSET VEO-IBD AND HLH

Abstract Mutations in syntaxin-binding-protein-2 (STXBP2) can result in NK cell dysfunction leading to a hyperinflammatory state including familial HLH and infantile onset inflammatory bowel disease (IBD). While the function of STXBP2 in NK cells and cytotoxic T cells has been well described, it is highly expressed in monocytes with unclear relevance. We report the case of an infant who presented with severe infantile onset diarrhea with an identified pathogenic mutation in STXBP2. We sought to utilize scRNA-Seq to study the impact of STXBP2 deficiency on monocyte transcription, with the goal of generating insight into the pathogenesis of disease. METHODS: Trio whole exome sequencing was performed. PBMCs were collected from the described patient (case), and two control groups: 3 patients with VEO-IBD, and 3 age matched healthy controls. Single cell RNA-Seq was performed using the 10x platform and data analysis was done using Seurat in R. RESULTS: A male infant presented at 1 week of age with diarrhea and metabolic acidosis. Endoscopic evaluation at 4 weeks of age showed histologic findings of colitis and marked epithelial cell changes, including cell rounding. WES identified a homozygous pathogenic mutation in STXBP2. Due to significant risk of HLH, he underwent evaluation for stem cell transplant. However, in the interim he developed severe HLH requiring ICU level care. He recovered following aggressive treatment and underwent HSCT at 4 months of age and retransplant for graft failure at 11 months of age. He is currently in endoscopic remission off therapy. We analyzed PBMCs from the case patient using single cell RNA-Seq, as compared to patients with VEO-IBD and age-matched controls. STXBP2 expression was most enriched in monocyte populations and reduced in the case patient compared to controls. 231 and 187 genes were differentially expressed in the case monocytes as compared to both controls. The case patient had a paucity of non-classical monocytes. Within the classical monocytes, differentially expressed genes showed enrichment of host defense, cytokine processes, and apoptotic processes. Within the intermediate monocytes, differentially expressed genes showed enrichment of chemotaxis pathways, antigen presentation and T cell activation processes. CONCLUSIONS: Mutations in STXBP2 are a life-threatening cause of fHLH and infantile onset IBD. We report a case of infantile onset IBD due to a homozygous mutation in STXBP2 with resolution of disease post HSCT. Transcriptional analysis of PBMCs from this patient reveals a paucity of non-classical monocytes in the peripheral blood, and differential regulation of genes implicated in host defenses, antigen presentation, chemotaxis and apoptosis. These results may suggest the role of monocyte function in pathogenesis of STXBP2 and in other forms of IBD.

P299 Ulcerative Colitis Severity Assessment through Abdominal Ultrasonography: A Diagnostic Accuracy Meta-analysis

Abstract Background Ulcerative colitis, a prevalent form of inflammatory bowel disease, necessitates a precise evaluation of disease severity. While effective, traditional diagnostic methods like colonoscopy are invasive and uncomfortable for patients. Abdominal ultrasonography offers a non-invasive alternative for this assessment, but its differential accuracy in evaluating disease severity in the right and left colon is not fully explored.This study aims to assess the diagnostic accuracy of abdominal ultrasonography in determining the severity of ulcerative colitis, focusing on its performance in the right and left colon. Methods A systematic review was conducted in PubMed, EMBASE, and the Cochrane Library, targeting studies up to June 2023. The selection criteria included studies that used abdominal ultrasonography for ulcerative colitis severity assessment, compared against histopathology or combined clinical, endoscopic, and radiological findings. Data analysis was performed using R software (version 4.0.3) with the mada package. This analysis focused on calculating sensitivity, specificity, diagnostic odds ratio, and positive and negative Likelihood Ratios for both the right and left colon, each with a 95% Confidence Interval. Results The search identified 5 studies with a total of 383 ulcerative colitis patients. In the right colon, the pooled sensitivity was 73.7% (95% CI, 57.6-85.2%, I2=0%), and specificity was 99.5% (95% CI, 1.6-100%, I2=0%). The diagnostic odds ratio was extremely high at 560.1 (95% CI, 0.04-6966551), with a positive Likelihood Ratio of 148.14 (95% CI, 0.01-1713586.1) and a negative Likelihood Ratio of 0.26 (95% CI, 0.15-0.45). In the left colon, sensitivity was higher at 93.7% (95% CI, 87.2-97%, I2=49.1%) with a specificity of 73.3% (95% CI, 41.8-91.3%, I2=70.9%). The diagnostic odds ratio for the left colon was 40.96 (95% CI, 8.67-193.62), with a positive Likelihood Ratio of 3.51 (95% CI, 1.31-9.42) and a negative Likelihood Ratio of 0.08 (95% CI, 0.04-0.19). Conclusion Abdominal ultrasonography shows promising results in assessing disease severity in ulcerative colitis, particularly in the left colon. The high specificity in the right colon is notable, but the wide confidence intervals suggest caution in interpretation, likely due to the small sample sizes and study variability. The left colon's more consistent and reliable performance indicates its suitability for routine clinical use in this region. This study highlights the need for further research with larger patient cohorts and standardized methodologies to solidify these findings and optimize ultrasonography’s role in ulcerative colitis management.

P421 The faecal biomarker LDN-051 is a novel tool for monitoring disease activity and therapeutic response in Inflammatory Bowel Diseases

Abstract Background Crohn’s disease and ulcerative colitis, two forms of inflammatory bowel disease (IBD) require lifelong treatment and patient monitoring. Current predictors of relapse and therapeutic success have limitations, therefore there is high unmet need to identify novel biomarkers in IBD. Monitoring approaches for IBD are mostly invasive, time-consuming, and expensive. Therefore, a simple, rapid, and non-invasive test, with ability to differentiate IBD from other gastrointestinal conditions and to monitor disease activity, will have important clinical implications. Our previous mucosal cytokine profiling identified that Plasminogen activator inhibitor type 1 (PAI-1) is expressed in IBD patients with active disease, but not in control. Therefore, our aim was to assess the utility of PAI-1 in monitoring disease activity and therapeutic response of IBD patients in different biological samples. Methods Serum, biopsy and faecal samples were collected from 132 IBD patients and 30 controls without IBD. ELISA method was used to define the level of PAI-1 in the mucosa, serum, and faecal samples and the serum CRP levels were also determined. For the mucosal gene expression analysis qRT-PCR was used. The correlation and ROC analyses were applied to observe the relationship between the disease activity and PAI-1 level. Results The applied screening approach detected significant higher expression of PAI-1 in active IBD. We demonstrated that the serum, mucosal and faecal PAI-1 concentration was significantly elevated in IBD patients showing clinical and endoscopic activity. Additionally, in responder patients the initial PAI-1 level decreased significantly upon successful therapy, whereas it remained unchanged in non-responders. We also showed that faecal PAI-1 selectively increases in active IBD patients, but not in other organic gastrointestinal diseases. In addition, the stability analysis of faecal PAI-1 showed that the protein was detectable up to one week at room temperature and 4ºC. The serum, mucosal and faecal PAI-1 level showed positive correlation to the endoscopic activity. ROC curves demonstrated that faecal PAI-1 showed a relatively high power to distinguish between active and control patients. However, the serum CRP level no reflected to the therapeutic response. Conclusion Our results suggest that serum, mucosal and faecal PAI-1 expression reflects to the disease activity in IBD, which could be used to disease monitoring and possibly therapeutic response. The correlation between the faecal PAI-1 level and the endoscopic activity promotes that it could be used as a novel non-invasive disease specific faecal biomarker in the IBD diagnosis.

Circulating VEGF and inflammatory bowel disease: a bidirectional mendelian randomization.

Introduction: Prior observational studies have suggested an association between circulating vascular endothelial growth factor (VEGF) levels and inflammatory bowel disease (IBD). This study sought to demonstrate the directionality of the association between circulating VEGF and particular forms of IBD as well as if there is a causal relationship between them. Methods: We collected summary data from relevant genome-wide association studies (GWASs) to assess the validity of causality, and a two-sample bidirectional Mendelian randomization (MR) study and sensitivity testing were performed to assess the causal relationship between circulating VEGF and IBD risk, including Crohn's disease and ulcerative colitis. Results: Our findings revealed a direct causal link between circulating VEGF and Crohn's disease (b 0.195, se 0.078, p < 0.013). However, neither circulating VEGF nor ulcerative colitis were shown to be causally linked (p > 0.025), nor was there proof of a reverse causal relationship from IBD to VEGF. Discussion: In conclusion, circulating VEGF shows a cause-and-effect relationship with Crohn's disease.

Colitis induced by IL-17A-inhibitors

BackgroundInterleukin (IL)-17A is essential for intestinal mucosal integrity, contributing to the prevention of detrimental immunity such as infectious colitis and inflammatory bowel disease (IBD). Indeed, neutralization of IL-17A has been abandoned as a therapeutic principle in IBD because of increased disease activity. However, it is controversial whether IL-17A inhibitors increase the risk of developing colitis in patients who do not have underlying IBD. Here, we present two cases of different forms of colitis that occurred during treatment with two IL-17A inhibitors, secukinumab and ixekizumab.Case presentationsWe report the case of a 35-year-old female with SAPHO (synovitis–acne–pustulosis–hyperostosis–osteitis) syndrome who was admitted due to severe colitis with bloody diarrhea, fever, abdominal pain and weight loss after receiving secukinumab for 3 months as well as the case of a 41-year-old male with psoriatic arthritis who presented himself to the outpatient clinic with bloody stools, abdominal pain and nausea 5 months after changing his therapy from secukinumab to ixekizumab. In both patients, treatment with IL-17A-inhibitors was stopped and tumor necrosis factor inhibitors were started. Both patients recovered, are clinically stable and show no more signs of active colitis.ConclusionThe role of IL-17A inhibitors in the pathogenesis of infectious colitis and new-onset IBD is not fully understood and requires further research. Patients receiving IL-17A-inhibitor therapy should be carefully screened and notified of the possible side effects.

Fecal Urgency in Ulcerative Colitis: Impact on Quality of Life and Psychological Well-Being in Active and Inactive Disease States

Ulcerative colitis (UC) is a chronic, relapsing-and-remitting, potentially progressive form of inflammatory bowel disease (IBD) with multidimensional and often negative effects on patients' lives. Fecal urgency, the sudden and compelling desire to defecate, often accompanied by impaired bowel control leading to frequent and urgent trips to the bathroom, is a distressing symptom, experienced by more than 50% of patients with UC.1 Physicians frequently underestimate the burden of fecal urgency on patients' lives, with ramifications ranging from disruption in daily activities, social interactions, and emotional distress with resultant impairment in quality of life (QoL).2,3.

Use of oral diet and nutrition support in management of stricturing and fistulizing Crohn's disease.

Crohn's disease (CD), a form of inflammatory bowel disease, involves chronic inflammation within the gastrointestinal tract. Intestinal strictures and fistulas are common complications of CD with varying severity in their presentations. Modifications in oral diet or use of exclusive enteral nutrition (EEN) are common approaches to manage both stricturing and fistulizing disease, although supporting research evidence is generally limited. In the preoperative period, there is strong evidence that EEN can reduce surgical complications. Parenteral nutrition (PN) is often utilized in the management of enterocutaneous fistulas, given that oral diet and EEN may potentially increase output in proximal fistulas. This narrative review highlights the current practices and evidence for the roles of oral diet, EEN, and PN in treatment and management of stricturing and fistulizing CD.