Classification Of Inflammatory Bowel Disease Research Articles

Lymphocytic colitis can be transcriptionally divided into channelopathic and inflammatory lymphocytic colitis.

The pathobiology of the non-destructive inflammatory bowel disease (IBD) lymphocytic colitis (LC) is poorly understood. We aimed to define an LC-specific mucosal transcriptome to gain insight into LC pathology, identify unique genomic signatures, and uncover potentially druggable disease pathways. We performed bulk RNA-sequencing of LC and collagenous colitis (CC) colonic mucosa from patients with active disease, and healthy controls (n=4-10 per cohort). Differential gene expression was analyzed by gene-set enrichment and deconvolution analyses to identify pathologically relevant pathways and cells, respectively, altered in LC. Key findings were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared our data with a previous cohort of ulcerative colitis and Crohn's disease patients (n=4 per group) to distinguish non-destructive from classic IBD. LC can be subdivided into channelopathic LC, which is governed by organic acid and ion transport dysregulation, and inflammatory LC, which is driven by microbial immune responses. Inflammatory LC displays an innate and adaptive immunity that is limited compared to CC and classic IBD. Conversely, we noted a distinct induction of regulatory non-coding RNA species in inflammatory LC samples. Moreover, compared with CC, water channel and cell adhesion molecule gene expression decreased in channelopathic LC, whereas it was accentuated in inflammatory LC and associated with reduced intestinal epithelial cell proliferation. We conclude that LC can be subdivided into channelopathic LC and inflammatory LC that could be pathomechanistically distinct subtypes despite their shared clinical presentation. Inflammatory LC exhibits a dampened immune response compared to CC and classic IBDs. Our results point to regulatory micro-RNAs as a potential disease-specific feature that may be amenable to therapeutic intervention.

HERMANSKY-PUDLAK SYNDROME-ASSOCIATED INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW ON CLINICAL MANIFESTATIONS AND INVESTIGATIONS INTO OPTIMAL MANAGEMENT

Abstract Hermansky-Pudlak Syndrome (HPS) is a rare autosomal condition resulting from a mutation in 1 of at least 7 different genes leading to the triad of tyrosine-positive oculocutaneous albinism, platelet dysfunction leading to prolonged bleeding time, and ceroid lipofuscin within the reticuloendothelial system. The latter of these can result in systemic derangements including renal failure, pulmonary fibrosis, cardiomyopathy, and a disabling granulomatous colitis. This colitis is a unique type of inflammatory bowel disease (IBD) with complications such as intestinal fistulization, ileitis, enterocolitis and perianal disease. There is data to suggest that HPS colitis is due to the development of classical IBD. However, optimal management remains undetermined. Our systematic review aims to analyze the clinical presentation behind HPS colitis, endoscopic versus histopathological findings, and ultimate treatment plans required for optimal management of this disease among HPS genotypes. A comprehensive literature review was conducted on patients with HPS and its associated colitis manifestations from inception to August 2023. Analyses on patient demographics, clinical presentation, HPS genotype, endoscopic versus histopathological findings, medical versus surgical interventions were thoroughly performed. Six cohort studies on HPS patients with coexisting colitis were identified. A total of 84 patients comprised these studies with mean age 32 +/- 9.65. Racial breakdowns were 68% Puerto Rican, 23% white, 4% Indian, 2% Mexican, 1% Honduran, and 1% African American. 59 patients had the HPS-1 genotype, 8 with HPS-3, 3 with HPS-4, and 1 with HPS-6. The most common presenting symptoms were hematochezia (37%), diarrhea (23%), abdominal pain (16%), and constipation (10%). Endoscopic evaluation showed normal gross findings in 65% of cases and abnormalities in only 35%. However, IBD-associated histopathological positivity was more prevalent with the most common findings being granulomas (33%), macrophages without colitis (19%), macrophages with colitis (15%), and lymphoid aggregates (10%). Medical therapy was initiated in 48 cases with the most common medications being steroids (46%), followed by anti-TNFa agents (40%), and immunomodulators (35%). 28 cases required surgical intervention with the most common operation performed being a (subtotal) colectomy and ileostomy. There were scattered cases of laparoscopic loop ileostomies, total colectomies, and proctocolectomies too. Interestingly, 10 patients received no intervention whatsoever. HPS-associated colitis is a debilitating condition that remarkably resembles IBD. There is no consensus on optimal therapy and many patients ultimately require operative intervention. The HPS-1 gene appears to be highly prevalent in this condition and younger patients are more affected, however more research is needed.

P112 Lymphocytic colitis can be transcriptionally divided into channelopathic and inflammatory lymphocytic colitis

Abstract Background The pathobiology of the non-destructive inflammatory bowel disease (IBD) lymphocytic colitis (LC) is poorly understood. We aimed to define an LC-specific mucosal transcriptome to gain insight into LC pathology, identify unique genomic signatures, and uncover potentially druggable disease pathways. Methods We performed bulk RNA-sequencing of LC and collagenous colitis (CC) colonic mucosa from patients with active disease, and healthy controls (n=4-10 per cohort). Differential gene expression was analyzed by gene-set enrichment and deconvolution analyses to identify pathologically relevant pathways and cells, respectively, altered in LC. Key findings were validated using reverse transcription quantitative PCR and/or immunohistochemistry. Finally, we compared our data to a previous cohort of ulcerative colitis and Crohn’s disease patients (n=4 per group) to distinguish non-destructive from classic IBD. Results LC can be subdivided into channelopathic LC, which is governed by organic acid and ion transport dysregulation; and inflammatory LC, which is driven by microbial immune responses. Inflammatory LC displays an innate and adaptive immunity that is limited compared to CC and classic IBD (Fig. 1). Conversely, we noted a distinct induction of regulatory non-coding RNA species in inflammatory LC samples. Moreover, compared to CC, water channel and cell adhesion molecule gene expression decreased in channelopathic LC, whereas it was accentuated in inflammatory LC and associated with reduced intestinal epithelial cell proliferation. Conclusion We conclude that LC can be subdivided into channelopathic LC and inflammatory LC that could be pathomechanistically distinct subtypes despite their shared clinical presentation. Inflammatory LC exhibits a dampened immune response compared to CC and classic IBDs. Our results point to regulatory micro-RNAs as a potential disease-specific feature that may be amenable to therapeutic intervention.

P1005 Dose escalated Infliximab in Inflammatory Bowel Disease - Crohn's Colitis Cure (CCC) Data Insights Program

Abstract Background Infliximab (IFX) is a monoclonal antibody targeting TNF-α and remains a cornerstone of management of Inflammatory Bowel Disease (IBD). A significant number of people with IBD on standard IFX therapy have persistent disease activity and require dose escalation (DE). In Australia and many other healthcare systems, funding through pharmaceutical benefits schemes is only available for standard dosing. We aim to evaluate the role of DE IFX and patient outcomes in a real-world cohort. Methods We performed a cross-sectional observational study using data from Crohn’s Colitis Care, a cloud-based IBD specific electronic medical record used in routine care in Australasia. Data were extracted in November 2023 from 14 private and public care centres. DE was defined as dosing interval <8 weeks and/or dosing >5mg/kg. We examined IBD outcomes prior to and 12 months post DE. Results A total of 1725 people received IFX, with DE in 762 (44.2%); 65% had Crohn’s Disease (CD), 33% had ulcerative colitis (UC) and 2% IBD-Unclassified (IBD-U), with a relatively even gender distribution (52.5% male). In the DE cohort, median age was 37 years (IQR 27-49); median age at diagnosis was 23 years (IQR 16-32) and median disease duration 11.6 years (IQR 5.8-17.3). DE and standard dose cohorts did not differ by IBD classification, gender, disease duration, age or age at diagnosis. Median drug level was higher 12-months post DE (8.16μg/ml vs 3.65 μg/ml). Faecal calprotectin (FCP) remission rate (FCP <250μg/g) was higher 12 months post DE, as was endoscopic remission rate and patient reported outcome remission (Table 1). The rate of systemic corticosteroids was lower 12 months post-DE than pre-DE. In the DE-IFX cohort, measures of healthcare utilisation were lower 12-months post-DE; hospitalisation (56 vs 146; p<0.001), surgical interventions (41 vs 61; p=0.040), endoscopic procedures (210 vs 397, p<0.001) and radiological investigations (243 vs 343; p<0.001). Conclusion Within a large Australasian IBD cohort, many individuals on IFX required DE. DE IFX was associated with improved measures of remission as well as a reduction in several measures of healthcare utilisation. These data will be used to undertake formal health economic analysis to determine the price points at which DE is cost-effective; additional data on quality of life and indirect healthcare costs will be important to include for a robust holistic assessment of value in care.

Involvement of Embryo-Derived and Monocyte-Derived Intestinal Macrophages in the Pathogenesis of Inflammatory Bowel Disease and Their Prospects as Therapeutic Targets.

Inflammatory bowel disease (IBD) is a group of intestinal inflammatory diseases characterized by chronic, recurrent, remitting, or progressive inflammation, which causes the disturbance of the homeostasis between immune cells, such as macrophages, epithelial cells, and microorganisms. Intestinal macrophages (IMs) are the largest population of macrophages in the body, and the abnormal function of IMs is an important cause of IBD. Most IMs come from the replenishment of blood monocytes, while a small part come from embryos and can self-renew. Stimulated by the intestinal inflammatory microenvironment, monocyte-derived IMs can interact with intestinal epithelial cells, intestinal fibroblasts, and intestinal flora, resulting in the increased differentiation of proinflammatory phenotypes and the decreased differentiation of anti-inflammatory phenotypes, releasing a large number of proinflammatory factors and aggravating intestinal inflammation. Based on this mechanism, inhibiting the secretion of IMs' proinflammatory factors and enhancing the differentiation of anti-inflammatory phenotypes can help alleviate intestinal inflammation and promote tissue repair. At present, the clinical medication of IBD mainly includes 5-aminosalicylic acids (5-ASAs), glucocorticoid, immunosuppressants, and TNF-α inhibitors. The general principle of treatment is to control acute attacks, alleviate the condition, reduce recurrence, and prevent complications. Most classical IBD therapies affecting IMs function in a variety of ways, such as inhibiting the inflammatory signaling pathways and inducing IM2-type macrophage differentiation. This review explores the current understanding of the involvement of IMs in the pathogenesis of IBD and their prospects as therapeutic targets.

PH Sensitive Quercetin Nanoparticles Ameliorate DSS-Induced Colitis in Mice by Colon-Specific Delivery.

Ulcerative colitis (UC) is a classic inflammatory bowel disease (IBD) that represents a serious threat to human health. As a natural flavonoid with multiple biological activities, quercetin (QCT) suffers from low bioavailability through limitations in chemical stability. Here, the study investigates the regulatory effects of quercetin nanoparticles (QCT NPs) on dextran sulfate sodium (DSS) induced colitis mice. Chitosan is modified to obtain N-succinyl chitosan (NSC) with superior water solubility. Nanoparticles composed of sodium alginate (SA) and NSC can encapsulate QCT after cross-linking, forming QCT NPs. In vitro drug release assays demonstrate the pH sensitivity of QCT NPs. Compared with free quercetin, QCT NPs have better therapeutic efficacy in modulating gut microbiota and its metabolites short chain fatty acid (SCFAs) to relieve DSS-induced colitis in mice, thereby alleviating colon inflammatory infiltration, increasing goblet cells density and mucus protein, ameliorating TNF-α, IL-1β, IL-6, IL-10, and Myeloperoxidase (MPO) levels, and recovering intestinal barrier integrity. pH sensitive QCT nanoparticles can reduce inflammatory reaction, improve gut microbiota, and repair intestinal barrier by targeting colon, thus improving DSS induced colitis in mice, providing reference for the treatment of colitis.

Diet high in linoleic acid dysregulates the intestinal endocannabinoid system and increases susceptibility to colitis in Mice

ABSTRACT Inflammatory bowel disease (IBD) is a multifactorial disease with increasing incidence in the U.S. suggesting that environmental factors, including diet, are involved. It has been suggested that excessive consumption of linoleic acid (LA, C18:2 omega-6), which must be obtained from the diet, may promote the development of IBD in humans. To demonstrate a causal link between LA and IBD, we show that a high fat diet (HFD) based on soybean oil (SO), which is comprised of ~55% LA, increases susceptibility to colitis in several models, including IBD-susceptible IL10 knockout mice. This effect was not observed with low-LA HFDs derived from genetically modified soybean oil or olive oil. The conventional SO HFD causes classical IBD symptoms including immune dysfunction, increased intestinal epithelial barrier permeability, and disruption of the balance of isoforms from the IBD susceptibility gene Hepatocyte Nuclear Factor 4α (HNF4α). The SO HFD causes gut dysbiosis, including increased abundance of an endogenous adherent invasive Escherichia coli (AIEC), which can use LA as a carbon source. Metabolomic analysis shows that in the mouse gut, even in the absence of bacteria, the presence of soybean oil increases levels of LA, oxylipins and prostaglandins. Many compounds in the endocannabinoid system, which are protective against IBD, are decreased by SO both in vivo and in vitro. These results indicate that a high LA diet increases susceptibility to colitis via microbial and host-initiated pathways involving alterations in the balance of bioactive metabolites of omega-6 and omega-3 polyunsaturated fatty acids, as well as HNF4α isoforms.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort.

Intestinal Behcet's Disease: A Review of the Immune Mechanism and Present and Potential Biological Agents.

Behcet's disease (BD) is a chronic and recurrent systemic vasculitis involving almost all organs and tissues. Intestinal BD is defined as BD with predominant gastrointestinal involvement, presenting severe complications such as massive gastrointestinal hemorrhage, perforation, and obstruction in some cases. To some extent, intestinal BD is classified as a member of inflammatory bowel disease (IBD), as it has a lot in common with classical IBD including Crohn's disease (CD) and ulcerative colitis (UC). Certainly, the underlying pathogenesis is not the same and dysregulation of immune function is believed to be one of the main pathogeneses in intestinal BD, although the etiology has not been clear up to now. Biological agents are an emerging category of pharmaceuticals for various diseases, including inflammatory diseases and cancers, in recent decades. Based on the deep understanding of the immune mechanism of intestinal BD, biological agents targeting potential pathogenic cells, cytokines and pathways are optimized options. Recently, the adoption of biological agents such as anti-tumor necrosis factor agents has allowed for the effective treatment of patients with refractory intestinal BD who show poor response to conventional medications and are faced with the risk of surgical treatment. In this review, we have tried to summarize the immune mechanism and present potential biological agents of intestinal BD.

Global attitudes on and the status of enteral nutrition therapy for pediatric inflammatory bowel disease.

Enteral nutrition (EN) is a diet-remission therapy for inflammatory bowel disease (IBD) that plays a more important role in children than adults. EN includes exclusive enteral nutrition (EEN), partial enteral nutrition (PEN), and maintenance enteral nutrition (MEN). However, EEN remains an unstandardized treatment for pediatric IBD. The types and methods of EN differ around the world. The current study reviewed the EN literature on children with IBD. A total of 12 survey studies were identified that analyzed the current state of EN use, including clinical opinions, implementation methods, treatment course, EEN formula, IBD classification, progress, dietary reintroduction, and patient feedback. The findings revealed that EEN has a strong effect on mild to moderate Crohn's disease (CD). The usage rates of this treatment in different sites were ileum/colon (Paris classification L3) > ileum (L1) > upper digestive tract (L4) > colon (L2) > perianal disease (P) > ulcerative colitis (UC) > extraintestinal lesions. The polymeric formula was the most used EN formulation. New EN diets include a CD exclusion diet (CDED), a specific carbohydrate diet (SCD), and a CD treatment-with-eating (CD-TREAT) diet. Children with IBD responded similarly to EEN administered orally or using a feeding tube. Most guidelines recommended 6-8 weeks of EEN treatment to induce remission. Many clinicians preferred to combine drug medications during EEN and recommended that MEN accounts for at least 25-35% of daily caloric intake. EN remains an unstandardized therapy that requires teamwork across disciplines.

S2704 A New Protein Losing Enteropathy: Autoimmune Cryptolytic Enterocolitis

Introduction: Protein losing enteropathy (PLE) can be classified into erosive, non-erosive, and increased interstitial pressure PLE. Presenting signs are often chronic non-bloody diarrhea, anasarca, abdominal pain, and weight loss. We present a complex case of a PLE presentation with a novel diagnosis. Case Description/Methods: A 30-year-old woman with a history of migraines presented with severe abdominal pain and chronic diarrhea. She was on long-term combined estrogen-progestin oral contraceptive pills (OCP) and chronic high dose non-steroidal anti-inflammatory (NSAID) medications. She was exposed to mycoplasma pneumoniae one month prior to presentation, without other infectious exposures. Laboratory tests were notable for hemoglobin 6 g/dL, albumin 0.5 g/dL, stool pathogen PCR negative, and fecal calprotectin >3000µg/g. Extensive infectious work up only revealed Mycoplasma IgM+. Inflammatory markers and alpha-1 anti-trypsin clearance were elevated, and she was found to have warm autoimmune hemolytic anemia. CT angiography excluded ischemia and vasculitis (autoimmune serologies were negative), revealing diffuse enterocolitis, confirmed on magnetic resonance enterography with ileal ulcers. Endoscopic evaluation revealed diffuse superficial ulcerations terminal ileum and colon with diffuse mucosal sloughing. Histopathology revealed diffusely injured crypts with crypt drop-out and minimal inflammation, without any findings to suggest infection, inflammatory bowel disease (IBD) or autoimmune enteritis (Figure). Normal B-cell switching studies excluded common variable immunodeficiency (CVID). Due to profound anasarca and inability to tolerate oral intake, albumin infusions and total parenteral nutrition were started. There was minimal response to systemic or topical steroids. Diarrhea was mildly improved with albumin repletion, and she was empirically started on vedolizumab. Discussion: Given the absence of classic IBD findings, negative infectious and immunological testing, we present the first case of autoimmune cryptolytic enterocolitis, a histopathologic diagnosis of unclear etiology and pathogenesis. The patient has responded to vedolizumab infusions as an empiric treatment for an IBD-like entity. Nevertheless, supporting the autoimmune component of this entity, is a possible concomitant potential pathway of molecular mimicry in the setting of post-mycoplasma infection along with chronic high dose NSAID and OCP exposure.Figure 1.: Terminal Ileum and Sigmoid Colon with Diffuse Crypt Dropout.

Identifying and understanding disease burden in patients with inflammatory bowel disease

ObjectivePhysicians tend to focus on biomedical targets while little is known about issues important to patients. We aimed to identify critical concepts impacting patients with inflammatory bowel disease (IBD).DesignWe performed...

Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease.

Interactions between the epithelium and the immune system are critical in the pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped the transcriptional landscape of human colonic epithelial organoids in response to different cytokines responsible for mediating canonical mucosal immune responses. By profiling the transcriptome of human colonic organoids treated with the canonical cytokines interferon gamma, interleukin-13, -17A, and tumor necrosis factor alpha with next-generation sequencing, we unveil shared and distinct regulation patterns of epithelial function by different cytokines. An integrative analysis of cytokine responses in diseased tissue from patients with IBD (n= 1,009) reveals a molecular classification of mucosal inflammation defined by gradients of cytokine-responsive transcriptional signatures. Our systems biology approach detected signaling bottlenecks in cytokine-responsive networks and highlighted their translational potential as theragnostic targets in intestinal inflammation.

Inflammatory bowel disease biomarkers of human gut microbiota selected via different feature selection methods.

The tremendous boost in next generation sequencing and in the “omics” technologies makes it possible to characterize the human gut microbiome—the collective genomes of the microbial community that reside in our gastrointestinal tract. Although some of these microorganisms are considered to be essential regulators of our immune system, the alteration of the complexity and eubiotic state of microbiota might promote autoimmune and inflammatory disorders such as diabetes, rheumatoid arthritis, Inflammatory bowel diseases (IBD), obesity, and carcinogenesis. IBD, comprising Crohn’s disease and ulcerative colitis, is a gut-related, multifactorial disease with an unknown etiology. IBD presents defects in the detection and control of the gut microbiota, associated with unbalanced immune reactions, genetic mutations that confer susceptibility to the disease, and complex environmental conditions such as westernized lifestyle. Although some existing studies attempt to unveil the composition and functional capacity of the gut microbiome in relation to IBD diseases, a comprehensive picture of the gut microbiome in IBD patients is far from being complete. Due to the complexity of metagenomic studies, the applications of the state-of-the-art machine learning techniques became popular to address a wide range of questions in the field of metagenomic data analysis. In this regard, using IBD associated metagenomics dataset, this study utilizes both supervised and unsupervised machine learning algorithms, (i) to generate a classification model that aids IBD diagnosis, (ii) to discover IBD-associated biomarkers, (iii) to discover subgroups of IBD patients using k-means and hierarchical clustering approaches. To deal with the high dimensionality of features, we applied robust feature selection algorithms such as Conditional Mutual Information Maximization (CMIM), Fast Correlation Based Filter (FCBF), min redundancy max relevance (mRMR), Select K Best (SKB), Information Gain (IG) and Extreme Gradient Boosting (XGBoost). In our experiments with 100-fold Monte Carlo cross-validation (MCCV), XGBoost, IG, and SKB methods showed a considerable effect in terms of minimizing the microbiota used for the diagnosis of IBD and thus reducing the cost and time. We observed that compared to Decision Tree, Support Vector Machine, Logitboost, Adaboost, and stacking ensemble classifiers, our Random Forest classifier resulted in better performance measures for the classification of IBD. Our findings revealed potential microbiome-mediated mechanisms of IBD and these findings might be useful for the development of microbiome-based diagnostics.

Precision Medicine in Inflammatory Bowel Diseases: Challenges and Considerations for the Path Forward

Precision Medicine in Inflammatory Bowel Diseases: Challenges and Considerations for the Path Forward

Natural NADH and FAD Autofluorescence as Label-Free Biomarkers for Discriminating Subtypes and Functional States of Immune Cells.

Immune cell activity is a major factor for disease progression in inflammatory bowel diseases (IBD). Classifying the type and functional state of immune cells is therefore crucial in clinical diagnostics of IBD. Label-free optical technologies exploiting NADH and FAD autofluorescence, such as multiphoton microscopy, have been used to describe tissue morphology in healthy and inflamed colon samples. Nevertheless, a strategy for the identification of single immune cell subtypes within the tissue is yet to be developed. This work aims to initiate an understanding of autofluorescence changes depending on immune cell type and activation state. For this, NADH and FAD autofluorescence signals of different murine immune cell subtypes under native conditions, as well as upon in vitro stimulation and cell death, have been evaluated. Autofluorescence was assessed using flow cytometry and multiphoton microscopy. Our results reveal significantly increased NADH and FAD signals in innate immune cells compared to adaptive immune cells. This allowed identification of relative amounts of neutrophils and CD4+ T cells in mixed cell suspensions, by using NADH signals as a differentiation marker. Furthermore, in vitro stimulation significantly increased NADH and FAD autofluorescence in adaptive immune cells and macrophages. Cell death induced a significant drop in NADH autofluorescence, while FAD signals were hardly affected. Taken together, these results demonstrate the value of autofluorescence as a tool to characterize immune cells in different functional states, paving the way to the label-free clinical classification of IBD in the future.

P708 Ileal involvement defined by Montreal classification in Crohn’s disease is associated with a distinct microbial composition in ileal and colonic mucosa

Abstract Background The Montreal classification of inflammatory bowel disease (IBD) recognizes distinct subgroups based on location of disease, age at onset and behaviour for Crohn’s disease (CD) and extent in ulcerative colitis (UC). CD with ileal involvement is in part genetically determined and tends to progress to surgery and to be more refractory to medical therapy compared to colonic disease location. We investigated the association of different aspects of the Montreal classification with the ileal and colonic mucosa-associated microbiota. Methods Healthy control (HC) and IBD patients underwent colonoscopy with biopsy samples taken from terminal ileum, ascending and sigmoid colon. Mucosal 16s rRNA gene profiling was analysed and an amplicon sequence variant table was generated and normalized. Patients with prior intestinal resection, IBD-unclassified and recent antibiotic exposure were excluded. Endoscopic activity was defined as a segmental Mayo endoscopic subscore > 0 in UC and a simple endoscopic score > 2 in CD. Blood samples were drawn for genotyping and a weighted genetic risk score (GRS) was built based on 169 IBD risk variants. Pooled ileal and colonic samples were analysed for taxonomic differential abundance (DA) among the variables of the Montreal classification using a linear mixed-effects model (MaAsLin2) with age, sex, biopsy site, endoscopic activity and GRS as covariates. P-values were corrected for false discovery rate (FDR) and < 5% was considered significant. Results A total of 546 biopsy samples from 201 IBD patients and 48 HC were analysed. The characteristics of the cohort and Montreal classification are depicted in the Table. At colonoscopy 168 samples (31.4%) showed endoscopic activity. The multivariate analysis revealed that the genera Agathobacter and Faecalibacterium, as well as the family Ruminococacceae and the order Oscillospirales were significantly reduced in CD with ileal involvement (L1+L3) when compared to either isolated colonic CD (L2), UC (any extent) and HC independent of age, sex, endoscopic activity, biopsy site, and GRS (Figure). Samples from UC and isolated colonic CD patients did not show differences in their microbial profile irrespective of biopsy site. No differences in DA were observed in subgroups based on age at onset and disease behaviour in CD or extent in UC. GRS was not associated with microbial composition. Conclusion These data suggest that CD with ileal involvement (Montreal L1+L3) is a major determinant of the tissue-associated microbial composition in both ileal and colonic mucosa irrespective of variables such as endoscopic activity and GRS. The reduction of several beneficial microbes in CD with ileal involvement might partially explain the more progressive phenotype in such patients.

P354 Immunological response to vaccination against SARS-COV-2 infection in Inflammatory Bowel Disease patients under immunosuppressive therapy: should we prioritize an additional booster injection?

BackgroundThe severe acute respiratory syndrome coronavirus, 2 (SARS-COV-2) infection may lead to the development of the novel coronavirus disease, 2019 (COVID-19). Currently, little to no data is available regarding safety and efficacy of SARS-COV-2 vaccination in Inflammatory Bowel Disease (IBD) patients, which may present differences between subgroups, as these patients may exhibit impaired innate and adaptive immune system responses. Lower immunological response could, in this specific population, require an additional booster injection.MethodsWe conducted a prospective study including adult patients with Crohn’s disease (CD) and Ulcerative Colitis (UC) who have undergone complete vaccination against SARS-COV-2 infection with BioNTech® vaccine. Patients with previous SARS-COV-2 infection were excluded. Medical data regarding age, sex, IBD classification and current medication for IBD were collected.A control group with healthy individuals matched for age and sex was also analyzed.Blood samples were collected, 30 days after complete vaccination to quantify IgG antibody titers for SARS-COV-2 in both groups (IBD and non-IBD).ResultsOur final sample included, 81 IBD and, 32 non-IBD patients, 55 (48.7%) of them females, with a mean age of, 40.2±13.0 years. From the IBD patients, 58(71.6%) had CD and, 23(28.4%) had UC.IBD patients had significantly lower anti-SARS-COV-2 IgG levels when compared to the control group (8950±9366 vs, 14834±11679 AU/mL; p=0.003).Regarding IBD medication, significant lower levels of SARS-COV-2 IgG antibodies when compared to control patients were found in patients under thiopurines (9074±9779 AU/mL; p=0.011); methotrexate (1987±2568 AU/mL; p=0.002); infliximab (7208±7276 AU/mL; p=0.001); and corticosteroids (1065±933 AU/mL; p=0.001). Additionally, patients under combined therapy (infliximab plus thiopurines) presented with significantly lower antibodies titers when compared to patients treated with thiopurines in monotherapy (8130±11048 vs, 10563±5680 AU/mL; p=0.039).No significant differences were found in IBD patients under salicylates (10195±7371 AU/mL; p=0.226); adalimumab (15644±21467 AU/mL; p=0.336); vedolizumab (10464±9087 AU/mL; p=0.286) and ustekinumab (11366±10016 AU/mL; p=0.390).ConclusionIBD patients presented with significantly lower anti-SARS-COV-2 IgG levels, 1 month after complete vaccination against SARS-COV-2 infection compared to healthy controls. Thiopurines, methotrexate, infliximab and corticosteroid treatment were associated with significantly lower antibodies levels. These findings may express the benefit of an additional booster injection in this population.

Histopathological Features of Monogenic Inflammatory Bowel Disease: Subanalysis of Systematic Review.

Histopathological Features of Monogenic Inflammatory Bowel Disease: Subanalysis of Systematic Review.

SERO-PREVALENCE OF EPSTEIN-BARR VIRUS IN IRAQI INFLAMMATORY BOWEL DISEASE.

The aim: Determine the frequency of anti-viral capsid antigen IgM, IgG and IgA in inflammatory bowel disease. Materials and methods: Case controlled study conducted during involved 60 Crohn's disease, 60 ulcerative colitis and 60 subjects as a control group with negative gastroin¬testinal symptoms. Diagnosis and disease classification were established according to Montreal disease classification of inflammatory bowel diseases. Measurement of serum anti-VCA IgM, IgG and IgA was done, using ELISA method. Results: The current results showed a higher frequency of EBV seropositivity among both Crohn's disease and ulcerative colitis 96.67% in comparison with controls 78.33. None statistical significance observed according to sex of patients. IgM were significantly associated with younger than 16 years 33.33%. IgA anti-VCA were significantly frequent within 17-40 years old comprising 100%. Patients with colonic and ileocolonic site of lesions were significantly have frequent anti-VCA IgA 96.43% and 96%. In ulcerative colitis IgM subtype of anti-VCA 35.71% frequent in extensive colitis. Anti-VCA IgG were statistically significant with moderate and severe ulcerative colitis cases 100%. Also, anti-VCA IgA associated with severity of ulcerative colitis 100% of mild cases, 96.43% of moderate cases and 100% of severe cases. Conclusion: EBV seropositivity were detected among IBD cases, however viral infection might be associated with distinct and severe cases that requires anti-viral therapy.