Inflammatory Bowel Disease Subtype Research Articles

Multi-Omics Characterization of Colon Mucosa and Submucosa/Wall from Crohn’s Disease Patients

Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn’s disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn’s disease and identifying potential biomarkers. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall, which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH.

Systematic review and meta-analysis: Impact of depression on prognosis in inflammatory bowel disease.

Depression is highly prevalent in patients with inflammatory bowel disease (IBD), which may affect the prognosis of IBD. This aimed to investigate the impact of depression on prognosis in IBD. A systematic literature search was performed in four databases (Medline, Embase, Web of Science, and PsycINFO) up to December 31, 2023. Studies were included if they investigated the impact of depression on prognosis in IBD. The primary outcome was flare in IBD, and secondary outcomes were hospitalization, readmission, emergency visits, surgery, and escalation of medical therapy. Relative risks (RRs) were utilized to estimate the risk in each of the above prognostic indicators. Fourteen cohort and 10 case-control studies matched our entry criteria, comprising 630 408 patients with IBD. Twenty-two of included studies were considered to have a low risk of bias. Depression was found to significantly increase the risk of flare (RR=1.37, 95% CI 1.16-1.63), hospitalization (RR=1.11, 95% CI 1.00-1.23), readmission (RR=1.32, 95% CI 1.04-1.67), emergency visits (RR=1.33, 95% CI 1.12-1.59), surgery (1.38, 95% CI 1.08-1.76), and escalation of medical therapy (RR=1.38, 95% CI 1.13-1.69) in IBD. Of note, patients with depression in ulcerative colitis had significant differences in readmission (RR=1.38, 95% CI 1.19-1.60) and escalation of medical therapy (RR=1.78, 95% CI 1.55-2.04). Additionally, the association was observed in patients with Crohn's disease in terms of flare (RR=1.47, 95% CI 1.08-2.01) and hospitalization (RR=1.20, 95% CI 1.03-1.40). Current evidence suggested that depression could significantly increase the risk of poor prognosis worsening in patients with IBD. However, the association varied in IBD subtypes.

Risk relationship between inflammatory bowel disease and urolithiasis: A two-sample Mendelian randomization study.

The causal genetic relationship between common parenteral manifestations of inflammatory bowel disease (IBD) and urolithiasis remains unclear because their timing is difficult to determine. This study investigated the causal genetic association between IBD and urolithiasis using Mendelian randomization (MR) based on data from large population-based genome-wide association studies (GWASs). A two-sample MR analysis was performed to assess the potential relationship between IBD and urolithiasis. Specific single nucleotide polymorphism data were obtained from GWASs, including IBD (n = 59957) and its main subtypes, Crohn's disease (CD) (n = 40266) and ulcerative colitis (UC) (n = 45975). Summarized data on urolithiasis (n = 218792) were obtained from different GWAS studies. A random-effects model was analyzed using inverse-variance weighting, MR-Egger, and weighted medians. Genetic predisposition to IBD and the risk of urolithiasis were significantly associated [odds ratio (OR), 1.04 (95% confidence interval [CI], 1.00-.08), P = 0.01]. Consistently, the weighted median method yielded similar results [OR, 1.06 (95% CI, 1.00-1.12), P = 0.02]. The MR-Egger method also demonstrated comparable findings [OR, 1.02 (95% CI, 0.96-1.08), P = 0.45]. Both funnel plots and MR-Egger intercepts indicated no directional pleiotropic effects between IBD and urolithiasis. CD was strongly associated with it in its subtype analysis [OR, 1.04 (95% CI, 1.01-1.07), P = 0.01], and UC was also causally associated with urolithiasis, although the association was not significant [OR, 0.99 (95% CI, 0.95-1.03), P = 0.71]. A unidirectional positive causal correlation was identified between IBD and urolithiasis, with varying degrees of association observed among the different subtypes of IBD. Recognizing the increased incidence of urolithiasis in patients with IBD is crucial in clinical practice. Early detection and surveillance of IBD, improved patient awareness, adoption of preventive strategies, and promotion of collaborative efforts among healthcare providers regarding treatment methodologies are vital for improving patient outcomes.

Probiotics for inflammatory bowel disease: Is there sufficient evidence?

Inflammatory bowel disease (IBD) refers to chronic inflammatory disorders of the gut. Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of IBD. Evidence suggests that the intestinal microbiota plays a role in the pathogenesis of IBD, so probiotics have garnered a lot of interest as a potential treatment or prevention for IBD. However, clinical evidence of the efficacy of probiotics is still debatable. We performed a literature review. An advanced search considered clinical studies on probiotic for IBD from inception to 2023 in PubMed, Embase, Cochrane Library, and Web of Science. In the treatment of UC with probiotics, only Escherichia coli Nissle 1917 for maintenance treatment of UC in remission, and Bifidobacterium and VSL#3 for induction of remission in patients with mild to moderately active UC have shown strong evidence. Currently, there are no definitive conclusions regarding the effectiveness of probiotics in CD. The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating intestinal flora balance, and modulating intestinal immune response. Differences in the benefits of probiotics between CD and UC may be attributable to the different lesion extent and immune-mediated pathophysiology. More robust randomized clinical trials are required to validate the efficacy and safety of diverse probiotic strains in IBD.

Evaluating the causal association between bronchiectasis and different types of inflammatory bowel disease: a two-sample Mendelian randomization study.

Previous observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn's disease (CD) and ulcerative colitis (UC) as IBD subtypes. A large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach. The IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively). This MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.

The role of goblet cells in Crohn' s disease.

The prevalence of Crohn's disease (CD), a subtype of inflammatory bowel disease (IBD), is increasing worldwide. The pathogenesis of CD is hypothesized to be related to environmental, genetic, immunological, and bacterial factors. Current studies have indicated that intestinal epithelial cells, including columnar, Paneth, M, tuft, and goblet cells dysfunctions, are strongly associated with these pathogenic factors. In particular, goblet cells dysfunctions have been shown to be related to CD pathogenesis by direct or indirect ways, according to the emerging studies. The mucus barrier was established with the help of mucins secreted by goblet cells. Not only do the mucins mediate the mucus barrier permeability and bacterium selection, but also, they are closely linked with the endothelial reticulum stress during the synthesis process. Goblet cells also play a vital role in immune response. It was indicated that goblet cells take part in the antigen presentation and cytokines secretion process. Disrupted goblet cells related immune process were widely discovered in CD patients. Meanwhile, dysbiosis of commensal and pathogenic microbiota can induce myriad immune responses through mucus and goblet cell-associated antigen passage. Microbiome dysbiosis lead to inflammatory reaction against pathogenic bacteria and abnormal tolerogenic response. All these three pathways, including the loss of mucus barrier function, abnormal immune reaction, and microbiome dysbiosis, may have independent or cooperative effect on the CD pathogenesis. However, many of the specific mechanisms underlying these pathways remain unclear. Based on the current understandings of goblet cell's role in CD pathogenesis, substances including butyrate, PPARγagonist, Farnesoid X receptor agonist, nuclear factor-Kappa B, nitrate, cytokines mediators, dietary and nutrient therapies were all found to have potential therapeutic effects on CD by regulating the goblet cells mediated pathways. Several monoclonal antibodies already in use for the treatment of CD in the clinical settings were also found to have some goblet cells related therapeutic targets. In this review, we introduce the disease-related functions of goblet cells, their relationship with CD, their possible mechanisms, and current CD treatments targeting goblet cells.

Exploring the causal relationship between Takayasu arteritis and inflammatory bowel disease using Mendelian randomization.

Takayasu arteritis (TA) and inflammatory bowel disease (IBD) are two distinct diseases; however, previous studies have reported many cases of IBD-TA coexistence. Additionally, the incidence of IBD in patients with TA is estimated to be significantly higher than the incidence in the general population. Therefore, the two diseases are anticipated to be linked. Mendelian randomization (MR) analysis assesses whether an exposure might causally affect an outcome by using genetic variants inherited randomly at conception, thereby reducing the impact of confounding and reverse causality. The present study aimed to investigate the potential causal relationship between TA and IBD using MR analysis. Two-sample MR analysis, in which TA and IBD were regarded as the exposure and outcome, respectively, was conducted to investigate whether the two diseases are causally related using the R TwoSampleMR package. Summary GWAS data of TA consisted of 516 Turkish cohorts and 462 controls, and 119 patients and 993 controls of European ancestry. Summary data of IBD was from a sub-study of the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC) that comprised 31,665 cases and 33,977 controls of European ancestry. Additionally, separate MR analyses stratified by the two major subtypes of IBD, Crohn's disease (CD) and ulcerative colitis (UC), were performed. Various statistical tests, including the intercept of MR-Egger regression, funnel plots, Cochran's Q tests, and leave-one-out sensitivity analyses, were employed to assess the presence of heterogeneity and horizontal pleiotropy among single nucleotide polymorphisms (SNPs). In the primary analysis using the inverse-variance weighted (IVW) method, the risk of developing IBD for a patient with TA compared to a non-TA control increased 1.053 times (Odds Ratio (OR) = 1.053, P = 0.065). The MR-Egger method (OR = 1.025, P = 0.470) yielded results consistent with this null finding. However, both the weighted median method (OR = 1.038, P = 0.002) and the weighted mode method (OR = 1.051, P = 0.009) identified a significant harmful causal effect. The MR outcomes from separate subgroup analyses slightly diverged from those of IBD and TA. Specifically, for CD, three methods indicated that TA is a risk factor: IVW estimated the OR as 1.045 (P = 0.032), MR-Egger as 0.997 (P = 0.957), weighed median as 1.028 (P = 0.021), and weighted mode as 1.031 (P = 0.022), respectively. This study represents one of the initial investigations into the potential causal association between TA and IBD. With three MR methods, including the primary IVW approach, indicating a notable effect on TA on CD, our analysis findings offer some indication that TA could be a contributing risk factor for CD.

Radiological biomarkers reflecting visceral fat distribution help distinguish inflammatory bowel disease subtypes: a multicenter cross-sectional study

ObjectivesTo achieve automated quantification of visceral adipose tissue (VAT) distribution in CT images and screen out parameters with discriminative value for inflammatory bowel disease (IBD) subtypes.MethodsThis retrospective multicenter study included Crohn’s disease (CD) and ulcerative colitis (UC) patients from three institutions between 2012 and 2021, with patients with acute appendicitis as controls. An automatic VAT segmentation algorithm was developed using abdominal CT scans. The VAT volume, as well as the coefficient of variation (CV) of areas within the lumbar region, was calculated. Binary logistic regression and receiver operating characteristic analysis was performed to evaluate the potential of indicators to distinguish between IBD subtypes.ResultsThe study included 772 patients (365 CDs, median age [inter-quartile range] = 31.0. (25.0, 42.0) years, 255 males; 241 UCs, 46.0 (34.0, 55.5) years, 138 males; 166 controls, 40.0 (29.0, 53.0) years, 80 males). CD patients had lower VAT volume (CD = 1584.95 ± 1128.31 cm3, UC = 1855.30 ± 1326.12 cm3, controls = 2470.91 ± 1646.42 cm3) but a higher CV (CD = 29.42 ± 15.54 %, p = 0.006 and p ˂ 0.001) compared to UC and controls (25.69 ± 12.61 % vs. 23.42 ± 15.62 %, p = 0.11). Multivariate analysis showed CV was a significant predictor for CD (odds ratio = 6.05 (1.17, 31.12), p = 0.03). The inclusion of CV improved diagnostic efficiency (AUC = 0.811 (0.774, 0.844) vs. 0.803 (0.766, 0.836), p = 0.08).ConclusionCT-based VAT distribution can serve as a potential biomarker for distinguishing IBD subtypes.Critical relevance statementVisceral fat distribution features extracted from CT images using an automated segmentation algorithm (1.14 min) show differences between Crohn’s disease and ulcerative colitis and are promising for practical radiological screening.Key points• Radiological parameters reflecting visceral fat distribution were extracted for the discrimination of Crohn’s disease (CD) and ulcerative colitis (UC).• In CD, visceral fat was concentrated in the lower lumbar vertebrae, and the coefficient of variation was a significant predictor (OR = 6.05 (1.17, 31.12), p = 0.03).• The differences between CD, UC, and controls are promising for practical radiological screening.Graphical

Increased prevalence of migraine in women with inflammatory bowel disease: A cross-sectional study.

Some studies have suggested an association between migraine and inflammatory bowel disease. We determined migraine prevalence in a cohort of patients with inflammatory bowel disease. Patients with inflammatory bowel disease aged 18-65 years were interviewed using an ad hoc headache questionnaire. Those who admitted a history of headache in the last year answered the three questions of the ID-Migraine questionnaire. Those who answered "yes" to the three of them were classified as "definite" and those who answered "yes" to two were classified as "probable" migraine. We interviewed 283 patients with inflammatory bowel disease. Of these, 176 (62.2%) had headache. Fifty-nine (20.8%; 95% CI 16.3-26.0%) met migraine criteria either definite (n = 33; 11.7%; 95% CI 8.2-16.0%) or probable (n = 26; 9.2%; 95% CI 6.1-13.2). When divided by gender, 12 men (9.6%; 95% CI 5.1-16.2%) and 47 women (29.8%; 95% CI 22.8-37.5%) met migraine criteria. The prevalence of migraine was increased in inflammatory bowel disease patients from the current cohort (20.8%) versus that reported for our general population for the same age group (12.6%; p < 0.0001). These differences remained significant in female inflammatory bowel disease patients (29.8% versus 17.2% in our general population; p < 0.0001), but not in males (9.6% in inflammatory bowel disease vs 8.0%; p = 0.30). Seventeen patients with inflammatory bowel disease (6.0%; 95% CI 3.54-9.44%) fulfilled chronic migraine criteria. There were no differences in migraine prevalence by inflammatory bowel disease subtypes. Migraine prevalence, including chronic migraine, seems to be increased in patients with inflammatory bowel disease. The fact that this association was stronger for women suggests an influence of sex-related factors.

Short noncoding RNAs as predictive biomarkers for the development from inflammatory bowel disease unclassified to Crohn's disease or ulcerative colitis.

Numerous pathogenic processes are mediated by short noncoding RNAs (sncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether sncRNAs can predict CD or UC among IBDU patients. 35 IBDU patients who were initially diagnosed with IBDU were included in this retrospective investigation; of them, 12, 15, and 8 were reclassified into CD (IBDU-CD), UC (IBDU-UC), or remained as IBDU (IBDU-IBDU), respectively. Eight IBD patients, were included as references. SncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95% CI: 60-97) in discriminating IBDU-CD from IBDU-UC. Based on the three sncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.

The gut ileal mucosal virome is disturbed in patients with Crohn’s disease and exacerbates intestinal inflammation in mice

Gut bacteriome dysbiosis is known to be implicated in the pathogenesis of inflammatory bowel disease (IBD). Crohn’s disease (CD) is an IBD subtype with extensive mucosal inflammation, yet the mucosal virome, an empirical modulator of the bacteriome and mucosal immunity, remains largely unclear regarding its composition and role. Here, we exploited trans-cohort CD patients and healthy individuals to compositionally and functionally investigate the small bowel (terminal ileum) virome and bacteriome. The CD ileal virome was characterised by an under-representation of both lytic and temperate bacteriophages (especially those targeting bacterial pathogens), particularly in patients with flare-up. Meanwhile, the virome-bacteriome ecology in CD ileal mucosa was featured by a lack of Bifidobacterium- and Lachnospiraceae-led mutualistic interactions between bacteria and bacteriophages; surprisingly it was more pronounced in CD remission than flare-up, underlining the refractory and recurrent nature of mucosal inflammation in CD. Lastly, we substantiated that ileal virions from CD patients causally exacerbated intestinal inflammation in IBD mouse models, by reshaping a gut virome-bacteriome ecology preceding intestinal inflammation (microbial trigger) and augmenting microbial sensing/defence pathways in the intestine cells (host response). Altogether, our results highlight the significance of mucosal virome in CD pathogenesis and importance of mucosal virome restoration in CD therapeutics.

Perceived value of computed tomography imaging for patients with inflammatory bowel disease in the emergency department: a Canadian survey

Abstract Background There are high rates of computed tomography (CT) utilization in the emergency department (ED) for patients with inflammatory bowel disease (IBD), despite guidelines recommending judicious use. We performed a national survey to better understand perceptions and practice patterns of Canadian physicians related to CT imaging in the ED. Methods Our survey was developed by a multistep iterative process with input from key stakeholders between 2021 and 2022. It evaluated Canadian gastroenterologists’, surgeons’, and emergency physicians’ (1) perceived rates of IBD findings detected by CT, (2) likelihood of performing CT for specific presentations and (3) comfort in diagnosing IBD phenotypes/complications without CT. Results A total of 208 physicians responded to our survey: median age 44 years (IQR, 37–50), 63% male, 68% academic, 44% emergency physicians, 39% gastroenterologists, and 17% surgeons. Compared with emergency physicians and surgeons, gastroenterologists more often perceived that CT would detect inflammation alone and less often IBD complications. Based on established rates in the literature, 13 (16%) gastroenterologists, 33 (40%) emergency physicians, and 21 (60%) surgeons overestimated the rates of at least one IBD complication. Although most physicians were more comfortable diagnosing inflammation compared to IBD complications without CT, gastroenterologists were significantly less likely to recommend CT imaging for non-obstructive/penetrating presentations compared with emergency physicians and surgeons with results that varied by IBD subtype. Conclusion This national survey demonstrates differences in physician perceptions and practices regarding CT utilization in the ED and can be used as a framework for educational initiatives regarding appropriate usage of this modality.

Association between inflammatory bowel disease and frailty: a two-sample Mendelian randomization study

BackgroundAn association has been identified between inflammatory bowel disease (IBD) and frailty; however, the causal nature of this connection remains uncertain. We consequently conducted a two-sample Mendelian randomization (MR) analysis to explore this particular association.MethodsWe acquired distinct datasets for inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), and frailty from the published genome-wide association studies (GWAS) database, meticulously selecting instrumental variables (IVs). Subsequently, we employed a bidirection MR to examine the causal relationship between IBD (including CD and UC) and frailty. We utilized statistical methods, with a primary emphasis on inverse-variance weighted (IVW), accompanied by a series of sensitivity analyses to confirm heterogeneity and pleiotropy influenced the outcomes of the MR.ResultsWe found positive causal effects of genetically increased frailty risk on IBD (OR: 1.015, 95% CI 1.005–1.025, P = 0.004). Furthermore, when scrutinizing specific IBD subtypes, both Crohn's disease (CD) and ulcerative colitis (UC) demonstrated an increased predisposition to frailty (OR: 1.018, 95% CI 1.01–1.027, P < 0.05) and (OR = 1.016, 95% CI 1.005–1.027, P < 0.05). Nevertheless, despite the consistent trends observed in the weighted median and MR-Egger regression analyses for both conditions, statistical significance remained elusive. Notably, the results of the inverse MR analysis did not establish an association between frailty and an elevated risk of IBD development.ConclusionsOur research indicates that IBD, encompassing both CD and UC, may augment the propensity for frailty. Clinical practitioners must prioritize early frailty assessment in individuals afflicted with inflammatory bowel disease, inclusive of Crohn's disease and ulcerative colitis, facilitating proactive measures and timely interventions. However, our findings do not provide evidence supporting a causal effect of frailty on IBD (including CD and UC). Consequently, further studies are essential to explore the intricate mechanisms that clarify the effect of frailty on IBD.

Long-term risk of myocarditis in patients with inflammatory bowel disease: a nationwide cohort study in Sweden.

Despite a suggested link between inflammatory bowel disease (IBD) and myocarditis, the association has not been well-established. This study aimed to investigate the long-term risk of myocarditis in patients with IBD. This nationwide cohort involved all patients with biopsy-confirmed IBD in Sweden (1969-2017) (n=83,264, Crohn's disease [CD, n=24,738], ulcerative colitis [UC, n=46,409], and IBD-unclassified [IBD-U, n=12,117]), general population reference individuals (n=391,344), and IBD-free full siblings (n=96,149), and followed until 2019. Primary outcome was incident myocarditis and secondary outcome was severe myocarditis (complicated with heart failure, death, or readmission). Flexible parametric survival models were used to estimate adjusted hazard ratios (aHR) and cumulative incidence of outcomes, along with 95% confidence intervals (CIs). During a median follow-up of 12 years, there were 256 myocarditis cases in IBD patients (incidence rate [IR]=22.6/100,000 person-years) and 710 in reference individuals (IR=12.9), with an aHR of 1.55 (95%CI: 1.33 to 1.81). The increased risk persisted through 20 years after IBD diagnosis, corresponding to one extra myocarditis case in 735 IBD patients until then. This increased risk was observed in CD (aHR=1.48 [1.11 to 1.97]) and UC (aHR=1.58 [1.30 to 1.93]). IBD was also associated with severe myocarditis (IR: 10.1 vs. 3.5; aHR=2.44 [1.89 to 3.15]), irrespective of IBD subtypes (CD: aHR=2.39 [1.43 to 4.01], UC: aHR=2.82 [1.99 to 4.00], and IBD-U: aHR=3.14 [1.55 to 6.33]). Sibling comparison analyses yielded similar results. Patients with IBD had an increased risk of myocarditis, especially severe myocarditis, for ≥20 years after diagnosis, but absolute risks were low.

ASSOCIATION OF HIDRADENITIS SUPPURATIVA AND INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract INTRODUCTION Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin condition that affects apocrine gland-bearing areas. Previous studies have demonstrated that HS is potentially associated with various autoimmune diseases. However, the relationship between HS and inflammatory bowel disease (IBD) has been unclear. METHODS A comprehensive literature search was conducted in electronic databases, PubMed and Embase, from inception to October 2023. We included published studies that provided estimated effects with a 95% confidence interval (CI) or raw data. The quality of the selected studies was evaluated using the Newcastle-Ottawa Scale. Crohn's disease and ulcerative colitis were analyzed separately. Data from each study were combined using the random-effects model and the generic inverse variance method to calculate the pooled odds ratio (OR) with a 95% confidence interval (CI) and I2 statistics. RESULTS Ten case-control studies involving 26,496,569 individuals (110,648 with HS and 26,385,921 without HS) were included in this meta-analysis. HS was associated with significantly higher risk in the IBD group (Pooled OR 2.18; 95% CI 1.42-3.32; P = 0.0003; I2 = 97%). Additionally, our analysis demonstrated a significant association between HS and ulcerative colitis (Pooled OR 1.49; 95% CI 1.26-1.78; P &amp;lt; 0.00001, I2 = 63%) and between HS and Crohn's disease (Pooled OR 1.79; 95% CI 1.33-2.40; P = 0.0001; I2 = 88%). CONCLUSION Our meta-analysis demonstrated that HS is significantly associated with IBD and IBD subtypes (Crohn's disease and ulcerative colitis). This finding emphasizes the need for awareness when patients with HS present with symptoms associated with IBD. Further studies should be conducted to understand the mechanism of the gut-skin axis in shared immune and inflammatory processes.

RETROSPECTIVE, SINGLE-CENTER, REAL-WORLD ANALYSIS OF BIOLOGIC AND IMMUNOMODULATOR THERAPY DISCONTINUATION IN ELDERLY IBD PATIENTS

Abstract BACKGROUND The population of elderly inflammatory bowel disease (IBD) patients is increasing each year, however use of immunomodulators and biologic therapy in this population remains low. Clinical IBD drug trials limit enrollment of elderly patients. This leads to poor understanding of medication adverse effects and long-term outcomes in this population. Medication sustainability reflects drug efficacy and safety of drugs, which lead to better adherence. The primary aim of this study was to compare the discontinuation rates of various IBD therapies in a cohort of elderly patients and provide some guidance on positioning therapies within this population. METHODS This was a single-center retrospective study conducted at an academic institution. Elderly IBD patients 60 years or older followed between 2016-2022 were included in the study. Patients had to be on either immunomodulator and/or biologic therapy. Chart review was performed to extract demographic data, duration of IBD therapy, and reasons for discontinuation. A Kaplan-Meier survival curve was generated per IBD therapy to depict drug sustainability stratified by reason for discontinuation. Statistical analysis was performed to assess for significant differences across survival curves. RESULTS A total of 224 elderly IBD patients were included in the study analysis. The cohort was comprised of 97 (43.3%) patients with ulcerative colitis (UC) and 127 (56.7%) patients with Crohn’s disease (CD). For both CD and UC, there were no significant differences in biologic drug discontinuation rates due to inadequate disease control (p=0.26 for CD; p=0.74 for UC). There was a significantly increased risk of elderly IBD patients stopping anti-TNF therapy due to medication adverse event compared to those on anti-integrin therapy (p=0.002) and immunomodulator therapy (p=0.003). CONCLUSIONS While the number of biologics used to treat IBD has increased in the last few decades, there is a paucity of studies examining real world sustainability of biologics particularly in elderly patients. With regards to effectiveness, our study showed that there was no significant difference among the three classes of biologics being discontinued due to poorly controlled disease. However, results of our study suggest that anti-TNF therapy is less sustainable in elderly IBD patients compared to other biologics and immunomodulator therapy due to patient experienced adverse events. Our results are pertinent to clinical practice as prescribing biologics other than anti-TNF therapy may increase an elderly patient’s therapy longevity and lead to optimized clinical outcomes. Figure 1 shows time to biologic discontinuation due uncontrolled disease by IBD subtype. For both Crohn’s disease and ulcerative colitis, there was no significant difference in drug survival per biologic with regards to discontinuation due to inadequately controlled disease. Figure 2 shows time to therapy discontinuation due to patient experienced adverse events. This included infections, infusion reactions, systemic reactions, laboratory abnormalities, financial burden, and non-compliance. There was a significantly increased risk of elderly IBD patients stopping anti-TNF over time due to adverse events compared to those on anti-integrin and immunomodulator therapy.

SHORT NONCODING RNAS AS PREDICTIVE BIOMARKERS FOR THE DEVELOPMENT FROM INFLAMMATORY BOWEL DISEASE UNCLASSIFIED TO CROHN’S DISEASE OR ULCERATIVE COLITIS

Abstract BACKGROUND Numerous pathogenic processes are mediated by short noncoding RNAs (ncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether short ncRNAs can predict CD or UC among IBDU patients. METHODS Of 35 IBDU patients initially diagnosed with IBDU, 12, 15, and eight were reclassified into CD(IBDU-CD), UC(IBDU-UC), or remained as IBDU(IBDU-IBDU) respectively. Eight IBD patients, were included as references. Short ncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR. RESULTS Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95 % CI: 60 - 97) in discriminating IBDU-CD from IBDU-UC. CONCLUSIONS Based on the three-short ncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.

P1135 Increased prevalence of migraine in women with inflammatory bowel disease: a cross-sectional study

Abstract Background Data on a possible comorbidity between migraine and inflammatory bowel disease (IBD) are controversial. Our aim was to determine the prevalence of migraine in a cohort of IBD patients. Methods We performed a cross-sectional study in a cohort of IBD patients at our IBD Unit. After informed consent, consecutive IBD patients aged 18-64 years were interviewed. Those who admitted a history of headache in the last year were asked to answer the three questions of the id-Migraine validated questionnaire. Those who answered "yes" to the three of them were classified as "definite" migraine and those who answered "yes" to two were classified as "probable" migraine. For all patients we collected demographic data, IBD subtype, disease duration, hospitalizations or surgeries and medical treatments. Migraine prevalence data of IBD patients were compared with reported local migraine prevalence data at 18-65 years of age (Cephalalgia 2011; 31: 463-70). Statistical analysis was done with SPSS®. Results We interviewed 283 consecutive IBD patients aged 20-65 years. Main characteristics of this population are described in table 1. Headache was present in 176 (62.2%) patients. Of those, 59 (20.8%; 95% CI 16.1-25.5%) met migraine criteria either definite (n= 33; 11.7%; 95% CI 8-15.4%) or probable (n=26; 9.2%; 95% CI 5.8-12.5). When divided by gender, 12 men (9.6%; 95% CI 4.4-14.) and 47 women (29.8%; 95% CI 22.7-36.9%) met migraine criteria. The prevalence of migraine was significantly increased in IBD patients (20.8%) versus that reported for our general population (12.6%; p= 0.0001). By sex, these differences remained significant in women (29.8% in IBD versus 17.2% in our general population; p=0.0001), but not in men (9.6% in IBD vs 8.0%; p=0.45) (Figure 1). By IBD subtypes, there were no significant differences between CD and UC in migraine prevalence (20.7% vs 19.6% respectively; p=0.58). Regarding IBD characteristics, men with total migraine had higher biologic treatment (66.7% vs 44% p=0.032), and immune mediated inflammatory diseases or extraintestinal manifestations of IBD (33.3% vs 9.6% p=0.0016), but the number of men with migraine was low (12). These associations were not significant for women, nor overall population (p&amp;gt;0.05). Additionally, we did not find any significant association in total migraine patients in the use of mesalazine, disease duration, immunomodulators, surgeries or hospitalizations, neither in total number of patients nor stratified by sex. Conclusion Migraine prevalence is higher in patients with IBD than general population, which is a further example of the bidirectional gut-brain interaction. The fact that this association was stronger for women suggests an influence of sex-related factors. ISCIII PI20/01358 and FEDER.

P842 Assessment of body composition parameters in patients with inflammatory bowel disease treated with biological therapy

Abstract Background There is growing evidence of the role of biological therapy (BT) in improving body composition parameters (BCP) in inflammatory bowel disease (IBD) patients. Since myopenia and high adiposity affect prognosis and could lead to treatment failure, there is the need for expanding the assessment of BCP in clinical practice beyond traditional measures like body mass index (BMI). Methods A cross-sectional study included 151 IBD patients treated with BT (80 males, 83 Crohn`s disease, 68 ulcerative colitis, mean age 37). Bioelectrical Impedance Analysis (InBody170) was done to estimate: body weight, BMI, skeletal muscle mass (SMM), body fat mass (BFM), percent body fat (PBF), fat free mass (FFM). Dividing SMM, FFM and BFM by height squared, we calculated the skeletal muscle mass index (SMI), fat-free mass index (FFMI) and fat mass index (FMI). Results In relation to BMI, 84 (55.6%) patients had healthy weight, 41 (27.2%) were overweight, 13 (8.6%) were obese and 13 (8.6%) were classified as underweight. Clinical remission was present in 139 (92.6%) patients. The average values of the measured BCP are as follows: body weight 71.7kg (41.4-123.7); body height 174.6±10.9cm; BMI 23.7kg/m2 (15.1-36.9); PBF 24.6% (5-48); SMI 9.7kg/m2 (6.3-13.5); FFMI 17.5kg/m2 (12.0-23.5); FMI 5.7kg/m2 (1.0-17.3). Muscle mass parameters were significantly higher in the group of patients treated with BT longer than 3 months (SMI p=0.01, FFMI p=0.02), while in the group of patients treated longer than 1 year we observed, apart from muscle mass parameters, a significant increase in adiposity parameters (FMI p=0.02, PBF p=0.06). [WU1] Patients who previously had the need for change of BT type had significantly higher values of FMI (p=0.04). Patients with extraintestinal manifestations (EIMs), compared to the group without EIMs, had statistically significantly lower values of body weight (p=0.02), SMI (p=0.01), and FFMI (p= 0.01). There was no statistically significant difference in BCP by IBD subtype, presence of clinical remission, BT type and protocol, previous operations, corticosteroids, mesalazines and azathioprine use. Conclusion The duration of treatment with BT can significantly affect muscle mass and adiposity parameters, leading to improved muscle mass parameters after 3 months of therapy, while an increase in adiposity markers is observed after 12 months of BT. Our findings suggest a potential association between EIMs and muscle mass alterations, as well as a relationship between the need for a change in BT type and higher adiposity parameters.

P1146 Familial Coaggregation of Inflammatory Bowel Disease with Cardiovascular Disease: a Nationwide Multigenerational Cohort Study

Abstract Background Genetics contribute to the development of both inflammatory bowel disease (IBD) and cardiovascular disease (CVD). Although an increased risk of CVD has been documented in IBD patients, little is known about the risk of CVD in family members of patients with IBD. Methods In this Swedish nationwide multigenerational cohort, we identified patients with biopsy-confirmed IBD (≥18 years) who had at least one family member living in Sweden at their date of diagnosis from 1969 through 2017. Each patient was matched with up to five IBD-free reference individuals from the general population. We then identified 205,642 first-degree relatives (FDRs: father, mother, full-siblings, offspring) and 44,790 spouses of IBD patients as well as 1,015,010 FDRs and 222,969 spouses of their reference individuals. These family members were followed from the later date of turning 18 years or their linked IBD patients/reference individuals being diagnosed/matched (i.e., index date), until the interested CVD outcome, heart transplant, emigration, death, or 31/12/2020, whichever came first. The primary outcome was any incident CVD and CVD mortality. Secondary outcomes included incident ischemic heart disease, heart failure, cerebrovascular disease, deep vein thromboembolism, pulmonary embolism, and atrial fibrillation/flutter. Flexible parametric survival models estimated the adjusted hazard ratio (aHR) with 95% confidence interval (CI). Results FDRs of IBD patients were at higher risks of incident CVD (aHR=1.04, 95%CI: 1.03 to 1.05) and CVD mortality (aHR=1.03 [1.00 to 1.06]) than FDRs of reference individuals (Figure 1). The increased risks were significant for almost all secondary outcomes, with point estimates hovering around a two to eight percent increased risk. Similar patterns were observed by IBD subtypes, sex, age and calendar period at index date, and family relationship of FDRs. In contrast, spouses demonstrated no increased risks of incident CVD or CVD mortality. Conclusion Relative risks of incident CVD and CVD mortality were only slightly increased in FDRs of patients with IBD, but not at all in spouses, suggesting no need for extra vigilance for CVD among family members of IBD patients.