Inflammatory Bowel Disease Controls Research Articles

Higher Intra-Abdominal Visceral Adipose Tissue Mass Is Associated With Lower Rates of Clinical and Endoscopic Remission in Patients With Inflammatory Bowel Diseases Initiating Biologic Therapy: Results of the Constellation Study

We sought to assess the association between intra-abdominal visceral adipose tissue (IA-VAT) and response to 3 different biologic drugs in patients with inflammatory bowel disease (IBD) and to investigate its effects on inflammatory cytokine expression, pharmacokinetics, and intestinal microbiota. We prospectively enrolled subjects with active IBD initiating infliximab, vedolizumab, or ustekinumab and a healthy control group. Baseline body composition (including IA-VAT as percent of total body mass [IA-VAT%]) was measured using GE iDXA scan. Primary outcome was corticosteroid- free deep remission at weeks 14-16, defined as Harvey Bradshaw Index <5 for Crohn's disease and partial Mayo score <2 for ulcerative colitis, with a normal C-reactive protein and fecal calprotectin. Secondary outcomes were corticosteroid-free deep remission and endoscopic remission (Endoscopic Mayo Score ≤1 in ulcerative colitis or Simple Endoscopic Score for Crohn's disease ≤2) at weeks 30-46. A total of 141 patients with IBD and 51 healthy controls were included. No differences in body composition parameters were seen between the IBD and healthy control cohorts. Patients with higher IA-VAT% were less likely to achieve corticosteroid-free deep remission (P < .001) or endoscopic remission (P= .02) vs those with lower IA-VAT%. Furthermore, nonresponders with high IA-VAT% had significantly higher serum interleukin-6 and tumor necrosis factor at baseline compared with responders and patients with low IA-VAT%. Drug pharmacokinetic properties and microbiota diversity were similar when comparing high and low IA-VAT% groups. Higher IA-VAT% was independently associated with worse outcomes. This association could be driven at least partially by discrete differences in inflammatory cytokine expression.

Severe acute respiratory syndrome coronavirus 2 infection does not worsen the course of inflammatory bowel disease in the long term.

The long-term outcome of inflammatory bowel disease (IBD) patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is under investigation. To assess, in a prospective study, whether a recent SARS-CoV-2 infection increases the risk of IBD relapse within 12 months. From March to April 2021, all IBD patients with recent (<2 months) SARS-CoV-2 infection (Cases) were enrolled. For each enrolled Case, four IBD Controls with no history of infection were considered. Clinical course of IBD was recorded for 12 months. Inclusion criteria: well defined diagnosis of IBD; age ≥18 and ≤85 years; 12-month follow-up; consent. Exclusion criteria: incomplete data; SARS-CoV-2 infection after enrollment. Additional inclusion criteria: recent SARS-CoV-2 infection for Cases; no history of SARS-CoV-2 infection for Controls. Data expressed as median [range]. Statistical analysis: Student-t-Test, Mann-Whitney U-test, χ2 test, multivariate logistic regression model [odds ratio (95% confidence interval)], Kaplan-Meier curves. One hundred forty-three IBD patients were enrolled. The analysis included 118 patients (22 met the exclusion criteria, three lost at follow-up): 29 (24.6%) Cases and 89 (75.4%) Controls. Demographic and clinical characteristics were comparable between groups. During the 12-month study, the frequency of IBD relapse was comparable between Cases and Controls [8 (27%) vs 19 (21%); P = 0.65]. At univariate analysis, SARS-CoV-2 infection was not a risk factor for IBD relapse within 12 months [1.5 (0.6-3.9); P = 0.34]. At multivariate analysis, IBD activity at baseline was the only risk factor for relapse [3.2 (1.1-9.1); P = 0.03]. Kaplan-Meier curves showed that survival from IBD relapse was comparable between Cases and Controls (P = 0.33). In a prospective 12-month study, a recent SARS-CoV-2 infection did not increase the risk of clinical relapse of IBD in the long term.

Adiponectin Levels in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

Introduction: Adipose tissue plays an important role in the pathogenesis of inflammatory conditions. The role of adipokines in inflammatory bowel disease (IBD) has been evaluated in the current literature with conflicting results. The aim of this study was to evaluate adiponectin levels in IBD patients, including Crohn’s disease (CD) and ulcerative colitis (UC), compared to controls, as well as further subgroup analyses. Hence, assessing the potential role of adiponectin as a surrogate marker. Methods: We performed a systematic electronic search on PubMed, Embase, Scopus, and Cochrane Library, including observational or interventional studies evaluating serum or plasma adiponectin levels in IBD patients in humans. The primary summary outcome was the mean difference (MD) in serum or plasma adiponectin levels between IBD patients versus controls. Subgroup analyses were conducted involving adiponectin levels in CD and UC compared to controls, as well as CD compared to UC. Results: A total of 20 studies were included in our qualitative synthesis and 14 studies in our quantitative synthesis, with a total population sample of 2,085 subjects. No significant MD in serum adiponectin levels was observed between IBD patients versus controls {−1.331 (95% confidence interval [CI]: −3.135–0.472)}, UC patients versus controls (−0.213 [95% CI: −1.898–1.472]), and CD patients versus controls (−0.851 [95% CI: −2.263–0.561]). Nevertheless, a significant MD was found between UC patients versus CD patients (0.859 [95% CI: 0.097–1.622]). Conclusions: Serum adiponectin levels were not able to differentiate between IBD, UC, and CD patients compared to controls. However, significantly higher serum adiponectin levels were observed in UC compared to CD patients.

Urolithiasis in patients with inflammatory bowel disease: A systematic review and meta-analysis of 13,339,065 individuals.

This study aimed to summarize the current literature regarding the prevalence of renal stones in patients with inflammatory bowel disease (IBD). Moreover, we aimed to evaluate the risk factors of urolithiasis in patients with IBD and the difference between patients with IBD and healthy controls in terms of urinary profile. On February 23, 2022, a computerized search was conducted on PubMed, OVID via MEDLINE, Web of Science, and Scopus using relevant keywords. Three independent reviewers performed 2-stage screening and data extraction. The National Institutes of Health tools were employed for quality assessment. Review Manager 5.4 software was used to calculate the mean difference (MD) between IBD patients and non-IBD in terms of urine profile using the Inverse-variance model and to estimate the odds ratio of reported risk factors for renal stones with the Generic Inverse-Variance model. Thirty-two articles (n = 13,339,065 patients) were included. The overall prevalence of renal stones in patients with IBD was 6.3%, 95% Confidence interval (4.8%-8.3%). The prevalence of urolithiasis was more common in Chron's disease vs Ulcerative colitis (7.9% vs 5.6%) and in old studies (1964-2009) than in more recent studies (2010-2022) (7.3% vs 5.2%), respectively. Compared to non-IBD patients, patients with IBD were associated with significantly lower urine volume (MD = -518.84 mL/day, P < .00001), calcium 24-hour urine (MD = -28.46 mg/day, P < .0001), citrate 24-hour urine (MD = -144.35 mg/day, P < .00001), sodium 24-hour urine (MD = -23.72 mg/day, P = .04), and magnesium 24-hour urine (MD = -33.25 mg/day, P < .00001). The overall prevalence of renal stones in patients with IBD was comparable to the general population. Patients with Chron's disease were associated with a higher prevalence of urolithiasis compared to Ulcerative colitis. Drugs that induce renal calculi should be stopped in high-risk patients.

Accuracy of ultrasound, bioelectrical impedance analysis and anthropometry as point-of-care measurements of skeletal muscle mass in patients with inflammatory bowel disease.

Disturbance of skeletal muscle mass has clinically important implications in patients with inflammatory bowel disease (IBD), but accurate quantification requires radiation-intense techniques. We aimed to compare point-of-care muscle assessments and their change with therapy with those using reference-standard whole-body dual energy X-ray absorptiometry (DXA). Adult patients with IBD and healthy controls underwent prospective assessment of muscularity by ultrasound of the dominant arm and both thighs, bioelectrical impedance analysis (BIA), anthropometric measurements, and DXA. Patients with active IBD were assessed again ≥13 weeks after initiating biologic induction therapy. In 54 patients with IBD and 30 controls, all muscle assessments correlated significantly with DXA-derived skeletal muscle index (SMI). In IBD, ultrasound of the arm and legs had the best agreement with DXA-derived SMI (mean difference 0 kg/m2 , 95% limits of agreement -1.3 to 1.3), while BIA overestimated DXA-derived SMI by 1.07 (-0.16 to +2.30) kg/m2 . In 17 patients who underwent biologic therapy, the percentage change in DXA-derived SMI correlated significantly with the percentage change in all other muscle assessment techniques. Responders (n = 9) increased SMI from baseline to follow-up when derived from DXA (mean 7.8-8.5 kg/m2 , p = 0.004), ultrasound of the arm and legs (300-343 cm2 , p = 0.021) and BIA (9.2-9.6 kg/m2 , p = 0.011). Ultrasound of the arm and legs out-performed other point-of-care methods in its accuracy of measuring muscle mass. All methods, except mid-arm circumference, were responsive to therapy-induced change. Ultrasound is the preferred non-invasive test for measuring muscle mass in patients with IBD.

Dietary Behaviors and Beliefs in Patients with Inflammatory Bowel Disease.

Due to a lack of clear dietary guidelines, patients with inflammatory bowel disease (IBD) self-impose dietary restrictions based on their own nutritional experiences. The aim of this study was to investigate dietary perceptions and behavior in IBD patients. A total of 82 patients (48 with Crohn's disease and 34 with ulcerative colitis) participated in this prospective, questionnaire-based study. Based on a literature review, the questionnaire was developed to investigate dietary beliefs, behaviors and food exclusions during IBD relapses and remission. The majority of patients (85.4%) believed that diet can be a trigger factor for IBD relapses, and 32.9% believed that diet initiates the disease. The majority of patients (81.7%) believed that they should eliminate some products from their diets. The most often-pointed-out products were spicy and fatty foods, raw fruits and vegetables, alcohol, leguminous foods, cruciferous vegetables, dairy products and milk. Most patients (75%) modified their diets after diagnosis, and 81.7% imposed food restrictions to prevent IBD relapses. The majority of patients avoided certain foods during relapses as well as to maintain remission of IBD, basing this on their own beliefs, inconsistently with current scientific knowledge. Patient education should be a key determinant in IBD control.

Ginkgo biloba Extract Preventively Intervenes in Citrobacter Rodentium-Induced Colitis in Mice.

Inflammatory bowel disease (IBD) represents a highly recurrent gastrointestinal disorder and global public health issue. However, it lacks effective and safe strategies for its control. Although Ginkgo biloba extract (GBE) has been suggested to exhibit preventive and therapeutic activity for the control of IBD, whether its activity is associated with its ability to modulate intestinal microbiota remains to be addressed. To investigate the effect of GBE on controlling IBD, a Citrobacter Rodentium (CR)-induced mouse colitis model was used, and then histopathological examinations, biochemical assays, immunohistochemistry, and immunoblotting were performed to detect histological changes, cytokines, and tight junction (TJ) proteins in the intestine samples. We also studied 16s rRNA to detect changes in intestinal microbiota and used GC-MS to determine the microbiota-related metabolites short chain fatty acids (SCFAs). The results of our studies revealed that pre-treatment with GBE was sufficient for protecting the animals from CR-induced colitis. As a mechanism for GBE activity, GBE treatment was able to modulate the intestinal microbiota and increase the SCFAs capable of decreasing the pro-inflammatory factors and up-regulating the anti-inflammatory factors while elevating the intestinal-barrier-associated proteins to maintain the integrity of the intestines. Accordingly, our results led to a strong suggestion that GBE should be seriously considered in the preventive control of CR-induced colitis and in the development of effective and safe therapeutic strategies for controlling IBD.

Identifying high-impact variants and genes in exomes of Ashkenazi Jewish inflammatory bowel disease patients

Inflammatory bowel disease (IBD) is a group of chronic digestive tract inflammatory conditions whose genetic etiology is still poorly understood. The incidence of IBD is particularly high among Ashkenazi Jews. Here, we identify 8 novel and plausible IBD-causing genes from the exomes of 4453 genetically identified Ashkenazi Jewish IBD cases (1734) and controls (2719). Various biological pathway analyses are performed, along with bulk and single-cell RNA sequencing, to demonstrate the likely physiological relatedness of the novel genes to IBD. Importantly, we demonstrate that the rare and high impact genetic architecture of Ashkenazi Jewish adult IBD displays significant overlap with very early onset-IBD genetics. Moreover, by performing biobank phenome-wide analyses, we find that IBD genes have pleiotropic effects that involve other immune responses. Finally, we show that polygenic risk score analyses based on genome-wide high impact variants have high power to predict IBD susceptibility.

Interleukin-4 Gene Polymorphisms in Romanian Patients with Inflammatory Bowel Diseases: Association with Disease Risk and Clinical Features.

Multiple cytokines have been studied for their role in the propagation of the inflammatory process related to inflammatory bowel diseases (IBD), but the role of interleukin-4 remains controversial. The aim of this study was to evaluate the role of two IL-4 gene single nucleotide polymorphisms (SNPs) in disease susceptibility and phenotypic expression. 2. A group of 160 patients with IBD (86CD/74UC) and 160 healthy controls were genotyped for IL-4 rs2243250/-590C/T and rs2070874/-34C/T using real-time polymerase chain reaction with TaqMan assay. 3. The analysis of IBD patients and controls revealed a significantly reduced frequency of the minor allele T of both SNPs in CD patients (p = 0.03, OR 0.55 and p = 0.02, OR 0.52) and for the entire IBD group (p = 0.01, OR 0.57 and p = 0.01, OR 0.55). Haplotype analysis identified the most frequent haplotype (rs2243250/rs2070874 CC) associated with a high risk for developing IBD (either UC or CD) (p = 0.003). IBD patients with extraintestinal manifestations had significantly increased frequency of the minor alleles T. We also found an association between the presence of allele C of rs2070874 and response to antiTNF treatment. 4. This is the first study to investigate the IL-4 gene's relation to IBD susceptibility conducted in Romania. Both SNPs were found to be associated with disease susceptibility and phenotypic features, such as extraintestinal manifestations and response to antiTNF agents.

Evaluating the clinical application of the immune cells' ratios and inflammatory markers in the diagnosis of inflammatory bowel disease.

Inflammatory Bowel Diseases (IBDs) are chronic inflammatory conditions of the gastrointestinal tract, including Crohn's disease (CD) and ulcerative colitis (UC). Developing methods for effective screening and diagnosis is extremely needed. Accordingly, this study aims to evaluate the potential of immune cells ratios in the diagnosis of IBD. This case-control study includes data from Jordan University Hospital (JUH) medical records for IBD patients with age- and gender-matched healthy controls. This study included 46 participants, of which 56.52% had IBD, 54.35% were males, with insignificant differences in sex, age, and body mass index (BMI) between IBD patients and controls (p>0.05). In the CD group, the variables with the highest sensitivity and specificity (HSS) were neutrophil-to-lymphocyte (NLR) (75%, 80%) and platelet-to-lymphocytes (PLR) (75%, 90%), in UC group; mean corpuscular hemoglobin (MCH) (80%, 80%). In CD group, the combinations giving the HSS were PLR+NLR (76%, 90.9%), C-reactive protein (CRP)+PLR (76%, 90.9%), and CRP+NLR (73.07%, 90%). In UC group, the combinations giving the HSS were erythrocyte sedimentation rate (ESR)+PLR (76.9%, 100%), PLR+MCH (74.07%, 100%), PLR+CRP (71.42%, 100%), and PLR+NLR (71.42%, 100%). Regression analysis identified five different combinations of significance in the diagnosis of CD and UC. Higher Youden's index was used and defined the most beneficial clinical combinations as NLR+PLR and CRP+PLR for CD, whereas ESR+PLR for UC. Implications to our study include the clinical application of immune cell ratios, inflammatory markers, and their different combinations along with patients' history and physical examination findings for easier, faster, and more cost-effective diagnosis of IBDs.

Hidradenitis suppurativa and inflammatory bowel disease in a nested case-control study.

Association between Hidradenitis Suppurativa (HS) and Inflammatory Bowel Disease (IBD) has been suggested. To assess characteristics of HS and IBD in patients with or without concomitant IBD. In a prospective, nested case-control study, each IBD patient with concomitant HS (Case) was retrospectively matched with 4 patients with HS and no IBD (Controls) for gender and age (±5 years).HS was classified according to the Hurley score and the International Hidradenitis Suppurativa Severity Score System (IHS4). Data were expressed as mean (Standard Deviation). Statistical analysis included Student-t Test or Mann-Whitney Test, χ2 test, univariate and multivariate logistic regression. The study population included 125 patients with HS: 25 with IBD, 100 matched Controls with no IBD. IBD group included 19 (76%) Crohn's disease and 6 (24%) Ulcerative Colitis patients. Obesity, familial HS and perianal HS were less frequent in Cases than in Controls (1[4%] vs 25(25%];p=0.02; 1[4%] vs 21(21%];p=0.04; 1[4%] vs 31(31%];p=0.005, respectively).HS was less severe in Cases when assessed by the IHS4 (5.9±4vs 9±6.7;p=0.04).Complete drug-induced response for HS was more frequent in IBD (13[53%] vs28 (28%]; p=0.04). Clinical characteristics of HS and of patients differed between Cases and Controls. Present findings suggest the need to appropriately search and assess skin lesions compatible with HS in IBD.

Evidence from clinical studies of the nutrological modulation of the gut microbiota in inflammatory bowel diseases: a systematic review

Introduction: The main risk factor for inflammatory bowel disease (IBD) is a positive family history in 10-25% of patients. Crohn's disease (CD) can affect individuals from 15 to 40 years old and from 50 to 80 years old, more frequently in women. Ulcerative colitis (UC) can start at any age. The pathogenesis of IBD is linked to genetically susceptible individuals, dysregulated gut microbiota (dysbiosis), chronic inflammation, and poor dietary patterns. Diet plays an important role in modulating the gut microbiota and can be applied as a therapeutic tool to improve the course of the disease. Objective: To carry out a systematic review of the main interactions between dietary therapy, gut microbiota, and inflammatory bowel disease, to elucidate the main clinical outcomes after nutrological treatment. Methods: The present study followed the international model of systematic review (PRISMA). Clinical studies were included, involving randomized controlled, prospective, and retrospective studies published from 2010 to 2022. Results: It was founded 87 studies on diet modulation in the control of IBD. These studies showed reductions in persistent intestinal symptoms, improvement of gut microbiota, reduction of inflammation markers, and improvement in quality of life, with p&lt;0.05 (95% CI). The studies were homogeneous (X2 = 98.9%), which increases the reliability of the clinical results on the dietary importance in the modulation of IBD. Conclusion: The important role of diet modulation in the control and even in the remission of IBD was evidenced.

Serum Levels of Lipoprotein Lipase Are Increased in Patients with Inflammatory Bowel Disease

Disruption of the lipid profile is commonly found in patients with inflammatory bowel disease (IBD). Lipoprotein lipase (LPL) is a key molecule involved in triglyceride metabolism that plays a significant role in the progression of atherosclerosis. In this study, our aim was to study whether serum LPL levels are different in IBD patients and controls and whether IBD features are related to LPL. This was a cross-sectional study that encompassed 405 individuals; 197 IBD patients with a median disease duration of 12 years and 208 age- and sex-matched controls. LPL levels and a complete lipid profile were assessed in all individuals. A multivariable analysis was performed to determine whether LPL serum levels were altered in IBD and to study their relationship with IBD characteristics. After the fully multivariable analysis, including cardiovascular risk factors and the changes in lipid profile that the disease causes itself, patients with IBD showed significantly higher levels of circulating LPL (beta coefficient 196 (95% confidence interval from 113 to 259) ng/mL, p < 0.001). LPL serum levels did not differ between Crohn's disease and ulcerative colitis. However, serum C-reactive protein levels, disease duration, and the presence of an ileocolonic Crohn's disease phenotype were found to be significantly and independently positively related to LPL. In contrast, LPL was not associated with subclinical carotid atherosclerosis. In conclusion, serum LPL levels were independently upregulated in patients with IBD. Inflammatory markers, disease duration and disease phenotype were responsible for this upregulation.

Identification of Specific Biomarkers and Pathways in the Treatment Response of Infliximab for Inflammatory Bowel Disease: In-Silico Analysis.

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. In biological therapy, infliximab became the first anti-tumor necrosis factor (TNF) agent approved for IBD. Despite this success, infliximab is expensive, often ineffective, and associated with adverse events. Prediction of infliximab resistance would improve overall potential outcomes. Therefore, there is a pressing need to widen the scope of investigating the role of genetics in IBD to their association with therapy response. In the current study, an in-silico analysis of publicly available IBD patient transcriptomics datasets from Gene Expression Omnibus (GEO) are used to identify subsets of differentially expressed genes (DEGs) involved in the pathogenesis of IBD and may serve as potential biomarkers for Infliximab response. Five datasets were found that met the inclusion criteria. The DEGs for datasets were identified using limma R packages through the GEOR2 tool. The probes' annotated genes in each dataset intersected with DGEs from all other datasets. Enriched gene Ontology Clustering for the identified genes was performed using Metascape to explore the possible connections or interactions between the genes. 174 DEGs between IBD and healthy controls were found from analyzing two datasets (GSE14580 and GSE73661), indicating a possible role in the pathogenesis of IBD. Of the 174 DEGs, five genes (SELE, TREM1, AQP9, FPR2, and HCAR3) were shared between all five datasets. Moreover, these five genes were identified as downregulated in the infliximab responder group compared to the non-responder group. We hypothesize that alteration in the expression of these genes leads to an impaired response to infliximab in IBD patients. Thus, these genes can serve as potential biomarkers for the early detection of compromised infliximab response in IBD patients.

Deoxycholic acid exacerbates intestinal inflammation by modulating interleukin-1β expression and tuft cell proportion in dextran sulfate sodium-induced murine colitis.

The etiology of inflammatory bowel disease (IBD) remains unclear. However, intestinal metabolism is known to be critical in the pathogenesis of IBD. Bile acid is one of the main intestinal metabolites, and its role in the pathogenesis of IBD is worthy of investigation. This study investigated the role of deoxycholic acid (DCA), a bile acid, in the pathogenesis of IBD. Peripheral serum metabolomics, fecal metabolomics, and microbiome analyses were performed on patients with IBD and healthy controls. Flow cytometry, real-time quantitative polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, immunohistochemical staining, and immunofluorescence analysis were used to evaluate cytokines in the inflamed colonic mucosa and immune cells and tuft cells in the intestine of mice with dextran sulfate sodium (DSS)-induced colitis. In total, 156 patients with IBD and 58 healthy controls were enrolled. DCA levels in the serum and feces of patients with IBD were significantly decreased compared to the controls. This decrease was associated with a decrease in the abundance of intestinal flora, including Firmicutes, Clostridia, Ruminnococcaceae, and Lachnospiraceae. Additionally, interleukin (IL)-1β levels in the serum of patients with active Crohn's disease were significantly increased compared with the healthy controls. Moreover, in DCA-treated DSS-induced mice, the expression of IL-1β and the proportion of CD3+ and CD4+ T cells increased while the number of intestinal tuft cells decreased, compared with the DSS group. In IBD patients, the decreased DCA levels in serum and fecal samples are associated with disturbances in gut microflora diversity and abundance. Possible mechanisms by which DCA affects immunity in DSS-induced murine colitis include increasing IL-1β secretion, reducing the number of tuft cells in the mucosa, and activating CD4+ and CD3+ T cells to exaggerate immune responses, consequently worsening intestinal inflammation.

High seroprevalence against SARS-CoV-2 in non-vaccinated patients with inflammatory bowel disease from Northern India.

The information on seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among patients with inflammatory bowel disease (IBD) and its comparison to healthy controls is sparse. We compared the seroprevalence rates in patients with IBD and healthy controls (HCs). Patients with IBD and HCs (contact of patients) underwent SARS-CoV-2 antibody testing (chemiluminescent immunoassay: Siemens kit IgG against antigen-S1RBD) between July 2020 and April 2021. Information on demography, disease characteristics, drug history and past history of SARS-CoV-2 infection were noted. Patients on 5-aminosalicylic acid or no treatment were considered not on immunosuppressants and those who had received steroids, thiopurines or methotrexate within sixmonths of inclusion were considered being on immunosuppressants. A total of 235 patients (51.9%, males; mean age, 38.7 ± 12.4years; median disease duration, 60months [interquartile range, IQR: 36-120]) (ulcerative colitis [UC]: 69.4%, Crohn's disease [CD]: 28.9%, IBD unclassified [IBDU]: 1.7%) and 73 HCs (mean age, 39.6 ± 10.9years, 80% males) were enrolled. Of the 235 patients, 128 (54.5%) patients were on immunosuppressants and 107 (45.5%) were noton immunosuppressants. Seventy-four (31.5%) patients were seropositive, of which two (0.9%) had previous history of SARS-CoV-2 infection and none received coronavirus disease-19 (COVID-19) vaccine. Seroprevalence between IBD patients and HCs (32% vs. 27%, p > 0.05) and between patients with and without immunosuppressants (28.1% vs. 36%, p > 0.05) was similar. Age, gender, disease type, duration and activity in the last sixmonths; and medication use were similar between patients with positive and negative serology. There was a progressive increase in seroprevalence from July 2020 to April 2021. Up to 1/3rd of patients with IBD were seropositive for immunoglobulin G (IgG) SARS-Cov-2 antibody indicating high seroprevalence in patients with IBD from Northern India.

P409 Using antidepressants for refractory symptoms of Inflammatory Bowel Disease: a prospective service evaluation

Abstract Background One third of patents with inflammatory bowel disease (IBD) have refractory gastrointestinal symptoms, such as pain and diarrhoea, even after exhaustion of medical therapies. A further 40% have persistent fatigue. Although antidepressants can improve such symptoms, their role in treatment-refractory IBD has not been studied. Methods We evaluated a Consultant Psychiatrist clinic for patients with refractory IBD symptoms. Patients were reviewed remotely over 3-6-month follow-up. For pain, we used duloxetine or venlafaxine first-line. For nausea and insomnia-driven fatigue, we used mirtazapine first-line. For refractory fatigue or diarrhoea, we used bupropion, reboxetine or vortioxetine. Ineffective medications were changed after 6-8 weeks. Antidepressants were combined and augmented with antipsychotic if required. The primary outcome was change in the self-report IBD Control Questionnaire, scored from 0 (poor) to 16 (good). Secondary outcomes were changes in depression (PHQ-9), anxiety (GAD-7), IBD Fatigue Scale and average daily bowel frequency. Data were presented as mean (SD) if parametric and median [interquartile range] if skewed. Changes over time were measured using 2-tailed paired t-tests (parametric) or Wilcoxon signed rank tests (skewed data). Results Of 62 patients with IBD offered antidepressants, 80.1% started treatment. Mean age was 41.8 years and mean IBD duration 16.6 years. Of these, 88% had Crohn’s disease, 70% were refractory to multiple biologics, 62% had previous bowel resection and 14% had intestinal failure. At baseline, 92% had severe fatigue (IBD-Fatigue &amp;gt;10), 52% had diarrhoea/high stoma output, 50% had pain and 18% nausea/vomiting. At baseline, 86% met ICD-10 criteria for moderate/severe depression and/or generalised anxiety disorder, and 26% had existing treatment-resistant depression. At follow-up, IBD Control score improved from 1.5 [0-4] to 5 [1.5-8] (p&amp;lt;0.001), as did depression (mean 24% reduction, p&amp;lt;0.001), anxiety (mean 28% reduction, p&amp;lt;0.001) and fatigue (mean 18% reduction, p=0.01). Although 27% of patients responded to first-line antidepressants, the rest required changes in treatment, combination therapy or augmentation. Ultimately, 51.5% were prescribed bupropion, reboxetine or vortioxetine, collectively in whom median bowel frequency fell from 6/day to 4/day (p&amp;lt;0.001). Only 8% could not tolerate antidepressants. Conclusion Even in very difficult-to-treat IBD, antidepressants can improve IBD control, depression, anxiety and fatigue. However, specialist- or combination antidepressants are often required in this specific group. Clinical services should consider expansion of psychiatry provision to improve IBD outcomes. Trials of antidepressants for patients with refractory IBD symptoms are needed.

P283 Awareness and perceptions of colorectal cancer risk and screening in Inflammatory Bowel Disease

Abstract Background Patients with inflammatory bowel disease (IBD) are at higher risk of developing colorectal cancer (CRC). Guidelines recommend periodic endoscopic surveillance to detect and manage dysplasia. We aimed to explore patient knowledge and perceptions of CRC risk and colonoscopic surveillance and identify potential barriers to surveillance practice. Methods A 44-item questionnaire was administered to IBD patients with colonic involvement attending gastroenterology clinics between July 2021 and April 2022. Results Of 418 respondents (demographics see table 1), 266 (64%) had ulcerative colitis and 145 (34%) had Crohn’s disease, with 177 (42%) diagnosed for ≥10 years. Two hundred and sixty-five (66%) patients rated their IBD control moderate/good (score ≥7/10), and 314 (75%) self-rated their understanding of IBD as good/excellent. Two hundred and ninety-eight patients (71%) recognised that CRC risk is higher in IBD but 83 (20%) felt the risk of CRC was lower in IBD or were unsure. Age (p=0.02), being a Crohn’s and Colitis UK (CCUK) member (p&amp;lt;0.001), patient rated IBD control (p=0.04) and self-rated understanding of IBD (p=0.01) were associated with better CRC risk awareness. One hundred and forty-nine (36%) respondents stated that their IBD healthcare professional (HCP) had previously discussed CRC risk with them; this was associated with better CRC knowledge (p=0.001). On multivariate analysis CCUK membership (OR 2.75; 95% CI 1.57- 4.83; p&amp;lt;0.001), prior HCP discussion (OR 1.57; 95% CI 0.85-2.87; p=0.01) and age ≥65 years (OR 0.3; 95% CI 0.09- 0.99; p=0.05) were predictive of greater CRC risk awareness. Concerning the most appropriate screening test for dysplasia, 369 patients (88%) stated colonoscopy, but only 29 (7%) were aware that colonic surveillance should commence 8-10 years after diagnosis; 153 (37%) recognised that optimal timing is when IBD is in remission. Patient reported information sources included gastroenterology HCPs (43%), patient support groups (28%), and patient leaflets (17%). The majority (78%) stated they would agree to have surveillance colonoscopy if advised by their HCP. Bowel preparation (50%) and discomfort (45%) were factors most likely to dissuade patients from agreeing to surveillance. Conclusion Patient knowledge of CRC risk and surveillance practice in IBD is variable. Modifiable factors associated with improved knowledge are discussion with HCPs and CCUK membership. Our findings underscore the need for better patient education to aid informed decision-making between patients and HCPs and improve adherence to colonoscopic surveillance.

P266 Potential oral microbial markers for differential diagnosis of Crohn’s disease and ulcerative colitis using machine learning model

Abstract Background Although the gut microbiome dysbiosis have independently been shown to be associated with inflammatory bowel disease (IBD), less is known about the relationship between oral microbiota and IBD. This study aimed to elucidate unique microbiome patterns in saliva from patients with IBD and investigate potential oral microbial markers for differentiating Crohn’s disease (CD) and ulcerative colitis (UC). Methods A multicenter, prospective cohort study recruited patients with IBD (UC, n=175, CD, n=127) and unrelated healthy controls (HC, n=100) to examine microbiota within the oral microenvironments. We used 16S rRNA gene sequencing data as features in training machine learning models (sPLS-DA, Sparse Partial Least-Squares Discriminant Analysis) to classify CD and UC. Results The V3-V4 amplicon reads of the saliva 16S rRNA sequencing data were taxonomically classified to a total of 2839 taxa (2270 genera) using Kraken2 based on Silva 138.1 reference. The sequences that were not classifiable down to family level were removed, and the samples having sequence depth less than 30000 were also removed, resulting in 2616 taxa for 390 samples (UC, n=168, CD, n=124, HC, n=98). The alpha diversity analysis revealed that the microbiome in IBD patients were significantly less rich than the healthy controls, while CD samples were slightly richer then UC samples (Figure 1, Observed, P = 0.01, Shannon index, p=0.02, Chao index, P=0.0001). An sPLS-DA model with 470 taxa as features was able to distinguish IBD vs control with high performance (AUROC=0.9774), while a separate sPLS-DA model with 130 features classified CD vs UC with an AUROC of 0.8755 (Figure 2,3). Conclusion Collectively, oral microbial profiles can serve as a diagnostic marker to discriminate patients with IBD from HC, and patients with CD from UC. As obtaining oral samples is relatively easier than obtaining stool or intestinal biopsies, an opportunity exists to perform oral microbiome-based studies in larger cohort sizes, preferentially in a longitudinal fashion.

OP28 Children and young adults with inflammatory bowel disease have an increased incidence and risk of developing mental health conditions: a UK population-based cohort study

Abstract Background While it is widely recognised that inflammatory bowel disease (IBD) is associated with depression and anxiety, the burden of mental health conditions in children and young adults with IBD remains unclear. This study assessed this burden using UK population-based data. Methods A retrospective observational study was performed using a large UK primary care dataset (Optimum Patient Care Research Database). Children and young adults aged 5–25 years diagnosed with IBD between 2010 and 2020 were propensity score matched with up to four population controls. The association between IBD and incident depression, anxiety disorder (AD), eating disorders, body image disorders, attention-deficit disorders, behavioural disorders, adjustment disorders, acute stress disorder, schizophrenia, bipolar disorder, post-traumatic stress disorder (PTSD), self-harm, parasuicide (including suicide), sleep disturbance and ‘any mental health condition’ (a composite consisting of all these mental health conditions) was investigated. Absolute risk was derived using Kaplan-Meier analysis. Relative risk of all outcomes up to 10-years in the IBD cohort versus controls was estimated using adjusted Cox proportional hazards models controlling for age, sex, socioeconomic status, ethnicity, and other conditions (asthma, atopic dermatitis, allergic rhinitis, thyroid disease, epilepsy, diabetes mellitus, cancer, juvenile idiopathic arthritis, systemic lupus erythematosus, ankylosing spondylitis, and psoriatic arthritis). Results 3,898 young patients with incident IBD were matched to 15,571 controls. IBD patients were significantly more likely to develop PTSD (adjusted Hazard Ratio [aHR] 2.47, 95% CI 1.23-4.94), eating disorders (aHR 1.85, 95% CI 1.05-3.26), self-harm (aHR 1.49, 95% CI 1.00-2.21), sleep disturbance (aHR 1.40, 95% CI 1.15-1.71), depression (aHR 1.34, 95% CI 1.16- 1.56), AD (aHR 1.25, 95% CI 1.06-1.48), and ‘any mental health condition’ (aHR 1.28, 95% CI 1.12-1.46) (Figure 1). In subgroup analysis, male sex, and IBD patients aged 12 to 17 appear to have the greatest additional risk for developing mental health conditions (Figure 2) and Crohn’s disease had a higher risk than ulcerative colitis (aHR 1.32, 95% CI 1.10-1.58 and aHR 1.19, 95% CI 0.95-1.49 respectively). Conclusion Young IBD patients have a significantly higher incidence and risk of new mental health conditions. Mental health remains a critically overlooked aspect of IBD patient management. Further research into identifying optimal monitoring tools and support for these patients is required to improve patient care.