Target In Inflammatory Bowel Disease Research Articles

The SERPINB4 gene mutation identified in twin patients with Crohn’s disease impaires the intestinal epithelial cell functions

Crohn’s disease (CD) is a chronic inflammatory autoimmune disease of unknown etiology. To identify new targets related to the initiation of CD, we screened a pair of twins with CD, which is a rare phenomenon in the Chinese population, for genetic susceptibility factors. Whole-exome sequencing (WES) of these patients revealed a mutation in their SERPINB4 gene. Therefore, we studied a wider clinical cohort of patients with CD or ulcerous colitis (UC), healthy individuals, and those with a family history of CD for this mutation by Sanger sequencing. The single-nucleotide difference in the SERPINB4 gene, which was unique to the twin patients with CD, led to the substitution of lysine by a glutamic acid residue. Functional analysis indicated that this mutation of SERPINB4 inhibited the proliferation, colony formation, wound healing, and migration of intestinal epithelial cells (IECs). Furthermore, mutation of SERPINB4 induced apoptosis and activated apoptosis-related proteins in IECs, and a caspase inhibitor significantly reduced these effects. Transcriptome sequencing revealed that the expression of genes encoding proinflammatory proteins (IL1B, IL6, IL17, IL24, CCL2, and CXCR2) and key proteins in the immune response (S100A9, MMP3, and MYC) was significantly upregulated during SERPINB4 mutant-induced apoptosis. Thus, the heterozygous SERPINB4 gene mutation causes the dysfunction of IECs, which would disrupt the intestinal epithelial barrier and contribute to the development of intestinal inflammation. The activation of SERPINB4 might represent a novel therapeutic target for inflammatory bowel disease.

Identifying novel inflammatory protein biomarkers and drug targets of inflammatory bowel disease by integrating Mendelian randomization, bioinformatics, and druggability analysis.

Inflammatory proteins have the potential to be used as therapeutic targets for inflammatory bowel disease (IBD). We conducted Mendelian randomization (MR) analysis to probe causal associations between 91 circulating inflammatory proteins and IBD in the discovery and replication cohorts. Subsequently, we conducted meta-analysis of results from two cohorts. We further conducted protein-protein interaction (PPI), enrichment analysis, and druggability evaluation to elucidate our results and prioritize potential therapeutic targets. By integrating data from two cohorts, we demonstrated that genetically predicted CD40 (odds ratio [OR] = 0.878, 95% confidence interval [CI] = 0.838-0.919) and C-X-C motif chemokine ligand (CXCL)5 (OR = 0.884, 95%CI = 0.841-0.930) decreased IBD risk. However, genetically predicted CXCL9 (OR = 1.184, 95%CI = 1.084-1.294), Interleukin (IL)-18 (OR = 1.140, 95%CI = 1.076-1.208), CD6 (OR = 1.096, 95%CI = 1.045-1.150), and 4E-binding protein 1 (4E-BP1) (OR = 1.154, 95%CI = 1.070-1.244) increased IBD risk. Moreover, genetically predicted CD40 (OR = 0.855, 95%CI = 0.801-0.912) decreased Crohn's disease (CD) risk. Genetically predicted fibroblast growth factor 21 (FGF21) (OR = 1.259, 95%CI = 1.135-1.397) and 4E-BP1 (OR = 1.202, 95%CI = 1.088-1.327) increased CD risk. We found no inflammatory protein associated with ulcerative colitis. Additionally, CD was significantly associated with elevated levels of three circulating inflammatory proteins, which are suggested to be the consequences of CD. PPI analysis demonstrated interactions between CXCL5, CXCL9, IL-18, CD40, and FGF21. Enrichment analysis indicated these identified proteins significantly enriched in inflammation-related signaling pathways, including interleukin signaling, cytokine signaling, and NF-κB pathway. Three proteins (CD40, IL-18, 4E-BP1) have been targeted for drug development on cancers and immune-related diseases, with potentials of therapeutic targets for IBD. Our results provide new biomarkers and drug targets for CD. Moreover, we further demonstrate critical roles of inflammation and immunity in the occurrence and development of IBD.

New treatment targets for inflammatory bowel disease?

The classic therapeutic goals of chronic inflammatory bowel disease (IBD) are, on the one hand, clinical remission and, on the other, the prevention of disease progression. The introduction of additional "targets" such as normalization of laboratory inflammation values, endoscopic and, possibly, histological mucosal healing and transmural parameters (ultrasound, magnetic resonance imaging and computed tomography) is intended to improve prognosis. Agood response to therapy is usually (also) evident from these targets, although the obligatory change in medication in order to improve the prognosis if the additional treatment goals are not achieved is not evidence-based. In the case of Crohn's disease and ulcerative colitis, individual and, if possible, personalized medicine should continue to be provided instead of strict target specifications.

The Multifaceted Impact of Bioactive Lipids on Gut Health and Disease.

Bioactive lipids have a multifaceted role in health and disease and are recognized to play an important part in gut immunity and disease conditions such as inflammatory bowel disease and colon cancer. Advancements in lipidomics, enabled by mass spectrometry and chromatographic techniques, have enhanced our understanding of lipid diversity and functionality. Bioactive lipids, including short-chain fatty acids, saturated fatty acids, omega-3 fatty acids, and sphingolipids, exhibit diverse effects on inflammation and immune regulation. Short-chain fatty acids like butyrate demonstrate anti-inflammatory properties, enhancing regulatory T cell function, gut barrier integrity, and epigenetic regulation, making them promising therapeutic targets for inflammatory bowel disease and colon cancer. Conversely, saturated fatty acids promote inflammation by disrupting gut homeostasis, triggering oxidative stress, and impairing immune regulation. Omega-3 lipids counteract these effects, reducing inflammation and supporting immune balance. Sphingolipids exhibit complex roles, modulating immune cell trafficking and inflammation. They can exert protective effects or exacerbate colitis depending on their source and context. Additionally, eicosanoids can also prevent pathology through prostaglandin defense against damage to epithelial barriers. This review underscores the importance of dietary lipids in shaping gut health and immunity and also highlights the potential use of lipids as therapeutic strategies for managing inflammatory conditions and cancer.

Targeting the Calcium-Sensing Receptor in Chemically Induced Medium-Grade Colitis in Female BALB/C Mice

Background/Objectives: The extracellular calcium-sensing receptor (CaSR) is a multifunctional receptor proposed as a possible drug target for inflammatory bowel disease. We showed previously that CaSR inhibition with NPS 2143, a negative allosteric modulator of the CaSR, somewhat ameliorated the symptoms of chemically induced severe colitis in mice. However, it was unclear whether the potential of CaSR inhibition to reduce colitis may have been overshadowed by the severity of the induced inflammation in our previous study. Therefore, we tested if CaSR inhibition could prevent medium-grade colitis. Methods: Female BALB/c mice were treated with NPS 2143 or a vehicle prior to the induction of colitis with 2.5% DSS. On the day of sacrifice, colons and plasma were collected. The histology score was determined based on hematoxylin-eosin-stained sections. Mucin content, proliferation (Ki67), and immune cell infiltration (CD3 and CD20) were quantified based on immunostainings. Gene expression was measured by RT-qPCR. Results: Treatment with NPS 2143 had no effect on the clinical symptom score of the mice. However, the colons of the mice in the treated group were significantly longer (p < 0.05), and NPS 2143 significantly reduced colon ulceration (p < 0.05). The treatment also significantly reduced the expression of COX2 in the proximal colon and IL-22 in the distal colon. The proliferation of cells in the lymph nodes was significantly lower after the treatment, but no difference was observed in the epithelial cells. Conclusions: In summary, while NPS 2143 had an anti-inflammatory effect on medium-grade colitis, this effect appeared to be milder than in severe colitis, as observed previously, indicating that the effectiveness of CaSR inhibition as an anti-inflammatory measure in the colon is proportional to disease severity.

Effectiveness of biologic therapies in achieving treatment targets in inflammatory bowel disease; real-world data from the Middle East (ENROLL study).

Real-world data assessing the effectiveness of biologics in patients with inflammatory bowel disease (IBD) in the Middle East are not well-established. In our study, we evaluated the effectiveness of biologic therapies in achieving clinical and endoscopic outcomes in biologic-naïve patients with IBD. A retrospective chart review was conducted at two tertiary care gastroenterology centers using electronic medical records of patients with moderate-to-severe IBD. The study period was from October 2017 to October 2023. Patients who were on infliximab, adalimumab, ustekinumab, or vedolizumab for 12 months were included in the analysis. The primary outcomes were the percentage of IBD-related hospitalizations or surgeries, achieving steroid-free remission, and endoscopic remission. A total of 422 patients were included in the study, of whom 264 (62.5%) patients had Crohn's disease (CD) and 158 (39%) had ulcerative colitis (UC). In patients with CD, endoscopic remission was attained in 51 (52%) of the patients on adalimumab, 38 (53%) of the patients on infliximab, 34 (56%) of the patients on ustekinumab, and 16 (51%) of the patients on vedolizumab. In patients with UC, endoscopic remission was attained in 40 (56%) of the patients on infliximab, 26 (61%) of the patients on adalimumab, 8 (55%) of the patients on ustekinumab, and 11 (53%) of the patients on vedolizumab. adalimumab, infliximab, ustekinumab, and vedolizumab were all effective in achieving clinical and endoscopic clinical outcomes in IBD in both UC and CD. The findings of this study suggest that the efficacy of biologics in a Middle Eastern population is similar to that in a Western population.

Clinical Approach to STRIDE-II in Real-Life Settings: Analysis and Practical Recommendations.

We aimed to (1) analyze the applicability of the updated Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations in real-world clinical practice, (2) identify barriers to their implementation, and (3) propose practical measures to overcome these obstacles. This qualitative study was based on a survey, a literature review, and expert opinions. Nine inflammatory bowel disease (IBD) experts identified 7 areas likely to be controversial or potential implementation barriers in daily clinical practice: endoscopy, histology, ultrasound, quality of life, biomarkers, symptom control, and patient-reported outcomes (PROs). Based on this, a survey was carried out among educational course participants. The experts discussed the literature review and survey results and proposed several statements and practical actions. A total of 55 gastroenterologists answered the survey. The reported difficulty level in reaching STRIDE-II treatment goals in clinical practice was high. Only 22% of participants performed clinical remission assessments using clinical indexes and PROs. Seventy percent of responders did not use fecal calprotectin cutoffs and considered changes from the previous levels instead. Mucosal healing as a long-term therapeutic goal was considered necessary to be individualized in specific patient subgroups (eg, elderly/fragile patients, multiple treatment failures, and last-line therapies). Other barriers, like the lack of access to imaging techniques or insufficient knowledge and skills among healthcare professionals, were detected. The experts suggested adding less stringent treatment goals and measurements, patient stratification, local adaptations, educational activities, and research. STRIDE-II recommendations face various implementation barriers needing careful evaluation in order to enhance their adoption in clinical practice, and ultimately improve outcomes in IBD patients.

The circadian rhythm as therapeutic target in inflammatory bowel disease

Abstract The primary objectives of the management of patients with inflammatory bowel disease (IBD) are to prevent IBD flares, prevent/delay disease progression and improve patients’ quality of life. To this end, one needs to identify risk factor(s) associated with flare-ups and disease progression. We posit that disruption of circadian rhythms is one of the key factors that is associated with risk of flare-up and disease progression. This hypothesis is based on published studies that show: (1) The circadian rhythm regulates many biological processes including multiple IBD-relevant biological processes that are critical in inflammatory/immune processes such as environment/microbe interaction, microbe/host interaction, intestinal barrier integrity and mucosal immunity—all central in the pathogenesis of IBD, and (2) Circadian machinery is the primary tool for the host to interact with the environment. Circadian misalignment results in a loss of preparedness of the host to respond and adjust to the environmental changes that could make the host more vulnerable to IBD flare-ups. In this review, we first provide an overview of circadian rhythms and its role in healthy and disease states. Then we present data to support our hypothesis that: (1) IBD patients have disrupted circadian rhythms (“social jet lag”) and (2) circadian misalignment and associated disrupted sleep decreases the resiliency of IBD patients resulting in microbiota dysbiosis, more disrupted intestinal barrier integrity and a more aggressive disease phenotype. We also show that circadian-directed interventions have a potential to mitigate the deleterious impact of disrupted circadian and improve IBD disease course.

Class A1 scavenger receptor antibody improves murine colitis by influencing macrophage and gut microbiota

This study aimed to investigate whether class A1 scavenger receptor (SR-A1) regulated macrophage polarization and gut microbial alteration during intestinal inflammation of colitis. A murine colitis model was established by feeding with dextran sulfate sodium (DSS), and treatment groups were injected intravenously with SR-A1 antibody. Results showed a preventive effect on colitis symptoms and fewer inflammatory cell infiltrates in treatment groups. Down-regulation of inflammatory cytokines and up-regulation of anti-inflammatory cytokine related to macrophages were seen in murine PBMC and LPMC after injected with SR-A1 antibody. The percentage of M2 macrophages was also elevated in treatment groups. In addition, SR-A1 antibody treatment resulted in the decreased apoptosis and increased proliferation of colonic epithelial cells. Other findings indicated that SR-A1 antibody injection could mediate its anti-inflammatory effect via inhibiting TLR4-MyD88-NF-kB signaling pathway and alterating the gut microbiota composition. Our research identified SR-A1 as a potential therapeutic target in inflammatory bowel disease (IBD).

Integrating plasma proteomics with genome-wide association data to identify novel drug targets for inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease that includes Crohn’s disease (CD) and ulcerative colitis (UC). Although genome-wide association studies (GWASs) have identified many relevant genetic risk loci, the impact of these loci on protein abundance and their potential utility as clinical therapeutic targets remain uncertain. Therefore, this study aimed to investigate the pathogenesis of IBD and identify effective therapeutic targets through a comprehensive and integrated analysis. We systematically integrated GWAS data related to IBD, UC and CD (N = 25,305) by the study of de Lange KM with the human blood proteome (N = 7213) by the Atherosclerosis Risk in Communities (ARIC) study. Proteome-wide association study (PWAS), mendelian randomisation (MR) and Bayesian colocalisation analysis were used to identify proteins contributing to the risk of IBD. Integrative analysis revealed that genetic variations in IBD, UC and CD affected the abundance of five (ERAP2, RIPK2, TALDO1, CADM2 and RHOC), three (VSIR, HGFAC and CADM2) and two (MST1 and FLRT3) cis-regulated plasma proteins, respectively (P < 0.05). Among the proteins identified via Bayesian colocalisation analysis, CADM2 was found to be an important common protein between IBD and UC. A drug and five druggable target genes were identified from DGIdb after Bayesian colocalisation analysis. Our study's findings from genetic and proteomic approaches have identified compelling proteins that may serve as important leads for future functional studies and potential drug targets for IBD (UC and CD).

Progress in research of TNF-like cytokine 1A as a therapeutic target for inflammatory bowel disease

Progress in research of TNF-like cytokine 1A as a therapeutic target for inflammatory bowel disease

Colonic Tuft Cells: The Less-Recognized Therapeutic Targets in Inflammatory Bowel Disease and Colorectal Cancer.

Tuft cells are more than guardian chemosensory elements of the digestive tract. They produce a variety of immunological effector molecules in response to stimulation; moreover, they are essential for defense against protozoa and nematodes. Beyond the description of their characteristics, this review aims to elucidate the potential pathogenic and therapeutic roles of colonic tuft cells in inflammatory bowel disease and colorectal cancer, focusing on their primarily immunomodulatory action. Regarding inflammatory bowel disease, tuft cells are implicated in both maintaining the integrity of the intestinal epithelial barrier and in tissue repair and regeneration processes. In addition to maintaining intestinal homeostasis, they display complex immune-regulatory functions. During the development of colorectal cancer, tuft cells can promote the epithelial-to-mesenchymal transition, alter the gastrointestinal microenvironment, and modulate both the anti-tumor immune response and the tumor microenvironment. A wide variety of their biological functions can be targeted for anti-inflammatory or anti-tumor therapies; however, the adverse side effects of immunomodulatory actions must be strictly considered.

Latest Intestinal Ultrasound Advancements In Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) treatment has evolved from monitoring clinical symptoms to targeting objective measurements of mucosal healing with endoscopic and radiologic imaging. It is well known that clinical symptoms do not match disease severity. Frequent evaluation with radiologic imaging is now the standard of care. Although Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) recommendations do not list radiographic targets as an endpoint due to the “limited ability of the currently available treatments to achieve transmural healing,” this will likely evolve over time particularly with the rapidly growing uptake of intestinal ultrasound (IUS) in clinical trials. For the time being, imaging is considered as an “adjuvant assessment rather than a formal treatment target.”

Cryo-EM structure of I domain-containing integrin αEβ7

The integrin family is a transmembrane receptor that plays critical roles in the cell-cell and cell-extracellular matrix adhesion, signal transduction such as cell cycle regulation, organization of the intracellular cytoskeleton, and immune responses. Consequently, dysfunction of integrins is associated with a wide range of human diseases, including cancer and immune diseases, which makes integrins therapeutic targets for drug discovery. Here we report the cryo-EM structure of the human α-I domain-containing full-length integrin αEβ7, which is expressed in the leukocytes of the immune system and a drug target for inflammatory bowel disease (IBD). The structure reveals the half-bent conformation, an intermediate between the close and the open conformation, while the α-I domain responsible for the ligand binding covers the headpiece domain by a unique spatial arrangement. Our results provide the structural information for the drug design targeting IBD.

The atypical IκB family member Bcl3 determines differentiation and fate of intestinal RORγt+ regulatory T-cell subsets

Peripherally induced regulatory T cells (pTregs) expressing the retinoic acid receptor-related orphan-receptor gamma t (RORγt) are indispensable for intestinal immune homeostasis. NF-κB family members regulate the differentiation of thymic Tregs and promote their survival in the periphery. However, the Treg-intrinsic molecular mechanisms controling the size of the pTregs in the intestine and associated lymphoid organs remain unclear. Here, we provide direct evidence that Bcl3 limits the development of pTregs in a T cell-intrinsic manner. Moreover, the absence of Bcl3 allowed for the formation of an unusual intestinal Treg population co-expressing the transcription factors Helios and RORγt. The expanded RORγt+ Treg populations in the absence of Bcl3 displayed an activated phenotype and secreted high levels of the anti-inflammatory cytokines IL-10 and TGFβ. They were fully capable of suppressing effector T cells in a transfer colitis model despite an intrinsic bias to trans-differentiate toward Th17-like cells. Finally, we provide a Bcl3-dependent gene signature in pTregs including altered responsiveness to the cytokines IL-2, IL-6, and TNFα. Our results demonstrate that Bcl3 acts as a molecular switch to limit the expansion of different intestinal Treg subsets and may thus serve as a novel therapeutic target for inflammatory bowel disease by restoring intestinal immune tolerance.

Targeting P2Y14R protects against necroptosis of intestinal epithelial cells through PKA/CREB/RIPK1 axis in ulcerative colitis

Purinergic signaling plays a causal role in the pathogenesis of inflammatory bowel disease. Among purinoceptors, only P2Y14R is positively correlated with inflammatory score in mucosal biopsies of ulcerative colitis patients, nevertheless, the role of P2Y14R in ulcerative colitis remains unclear. Here, based on the over-expressions of P2Y14R in the intestinal epithelium of mice with experimental colitis, we find that male mice lacking P2Y14R in intestinal epithelial cells exhibit less intestinal injury induced by dextran sulfate sodium. Mechanistically, P2Y14R deletion limits the transcriptional activity of cAMP-response element binding protein through cAMP/PKA axis, which binds to the promoter of Ripk1, inhibiting necroptosis of intestinal epithelial cells. Furthermore, we design a hierarchical strategy combining virtual screening and chemical optimization to develop a P2Y14R antagonist HDL-16, which exhibits remarkable anti-colitis effects. Summarily, our study elucidates a previously unknown mechanism whereby P2Y14R participates in ulcerative colitis, providing a promising therapeutic target for inflammatory bowel disease.

Exploring potential biomarkers and therapeutic targets in inflammatory bowel disease: insights from a mega-analysis approach.

Understanding the molecular pathogenesis of inflammatory bowel disease (IBD) has led to the discovery of new therapeutic targets that are more specific and effective. Our aim was to explore the molecular pathways and genes involved in IBD pathogenesis and to identify new therapeutic targets and novel biomarkers that can aid in the diagnosis of the disease. To obtain the largest possible number of samples and analyze them comprehensively, we used a mega-analysis approach. This involved reprocessing raw data from multiple studies and analyzing them using bioinformatic and machine learning techniques. We analyzed a total of 697 intestinal biopsies of Ulcerative Colitis (n = 386), Crohn's disease (n = 183) and non-IBD controls (n = 128). A machine learning analysis detected 34 genes whose collective expression effectively distinguishes inflamed biopsies of IBD patients from non-IBD control samples. Most of these genes were upregulated in IBD. Notably, among these genes, three novel lncRNAs have emerged as potential contributors to IBD development: ENSG00000285744, ENSG00000287626, and MIR4435-2HG. Furthermore, by examining the expression of 29 genes, among the 34, in blood samples from IBD patients, we detected a significant upregulation of 12 genes (p-value < 0.01), underscoring their potential utility as non-invasive diagnostic biomarkers. Finally, by utilizing the CMap library, we discovered potential compounds that should be explored in future studies for their therapeutic efficacy in IBD treatment. Our findings contribute to the understanding of IBD pathogenesis, suggest novel biomarkers for IBD diagnosis and offer new prospects for therapeutic intervention.

Targeted delivery of Fc-fused PD-L1 for effective management of acute and chronic colitis

The PD-1/PD-L1 pathway in mucosal immunity is currently actively explored and considered as a target for inflammatory bowel disease (IBD) treatment. However, systemic PD-L1 administration may cause unpredictable adverse effects due to immunosuppression. Here we show that reactive oxygen species (ROS)-responsive nanoparticles enhance the efficacy and safety of PD-L1 in a mouse colitis model. The nanoparticles control the accumulation and release of PD-L1 fused to Fc (PD-L1-Fc) at inflammatory sites in the colon. The nanotherapeutics shows superiority in alleviating inflammatory symptoms over systemic PD-L1-Fc administration and mitigates the adverse effects of PD-L1-Fc administration. The nanoparticles-formulated PD-L1-Fc affects production of proinflammatory and anti-inflammatory cytokines, attenuates the infiltration of macrophages, neutrophils, and dendritic cells, increases the frequencies of Treg, Th1 and Tfh cells, reshapes the gut microbiota composition; and increases short-chain fatty acid production. In summary, PD-L1-Fc-decorated nanoparticles may provide an effective and safe strategy for the targeted treatment of IBD.

ARGINASE 2 AMELIORATES EXPERIMENTAL COLITIS THROUGH ANTIOXIDANT EFFECTS VIA SPERMIDINE PRODUCTION

Abstract BACKGROUND Spermidine which is a type of polyamine, shows elevated levels in patients with ulcerative colitis and is implicated in the pathogenesis of ulcerative colitis (UC). Arginase 2 (ARG2) plays a critical role in spermidine production. This study aimed to determine the role and mechanism of endogenous spermidine by using ARG2-deficient mice. METHODS The protective role of spermidine against oxidative stress was examined by intracellular reactive oxygen species levels and cell viability. The physiological role of spermidine was investigated using Arg2 knockdown cells with reduced spermidine. The importance of ARG2 in inflammation was examined in the dextran sulfate sodium-induced colitis model. Protein expression levels of ARG2 and accumulation of spermidine in patients with UC were evaluated by immunohistochemistry of the rectum. RESULTS ARG2 protein expression and the accumulation of spermidine were upregulated in the rectum of mice with dextran sulfate sodium colitis. Spermidine upregulated antioxidant genes in the cells. Arg2 knockdown cells showed reduced antioxidant activity. Dextran sulfate sodium colitis was more severe in Arg2-deficient mice, and organoids derived from Arg2-deficient mice showed diminished tolerance to oxidative stress. Furthermore, in the rectum of patients with UC, ARG2 and spermidine expression levels were higher in the active phase than in the remission phase. CONCLUSIONS Endogenous spermidine in the intestinal epithelium induced by ARG2 has a protective role in colitis. Spermidine may be a promising new therapeutic target for inflammatory bowel disease.

PATIENT PERCEPTIONS OF ENDOSCOPIC TESTING IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE

Abstract BACKGROUND Inflammatory bowel disease (IBD) is associated with significant patient and societal burden. Treatments for IBD have traditionally focused on symptom management. However, clinical guidelines (Selecting Therapeutic Targets in Inflammatory Bowel Disease [STRIDE] II) now recommend treat-to-target approaches. Mucosal healing on endoscopy is becoming a key prognostic parameter in the management of IBD. In light of new guidelines, we aimed to qualitatively assess patient understanding of, and perspectives on, endoscopic measures in the context of disease monitoring and assessing treatment impact. METHODS Twenty patients diagnosed with IBD across the United States, United Kingdom, Spain, Italy, and France participated in TeleWebs (web-enabled phone interviews; United Kingdom, Spain, Italy, France) or a 5-day online bulletin board exchange (United States) discussing their condition and experiences. Specific information regarding disease history, conversations with physicians, experiences with endoscopy, and reactions to information shared on endoscopy were captured over a 5-day period. All respondents were recruited from double opt-in volunteer consumer market research panels. RESULTS Patients generally link disease remission to the absence of symptoms. Knowledge and perceptions of endoscopic measurements are largely driven by their physician perspectives and explanation to patients. Some patients are aware of healthy mucosa as a key part of remission, while others have no concept of the term. Patients report they find it psychologically reassuring to know that they are “healthy inside”. Due to its value, most patients are willing (5.7 on a 1 to 7 Likert Scale) to undergo endoscopy annually, but would be reluctant to do so more frequently. Table 1 outlines barriers and drivers reported by patients on the adoption of endoscopy. CONCLUSION The insight from this study provides understanding of patient perceptions of endoscopy and its place in treating their IBD. This study demonstrates that despite the barriers to the use of endoscopy, patients recognize its clinical relevance for disease management and are willing to periodically undergo a procedure.