Inflammatory Bowel Disease Research Research Articles

Challenges in IBD Research 2024: Novel Technologies.

Novel technology is one of the five focus areas of the Challenges in Inflammatory Bowel Disease (IBD) Research 2024 document. Building off the Challenges in IBD Research 2019 document, the Foundation aims to provide a comprehensive overview of current gaps in IBD research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of a multidisciplinary collaboration from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization. Specifically, the Novel Technologies section focuses on addressing key research gaps to enable interception and improve remission rates in IBD. This includes testing predictions of disease onset and progression, developing novel technologies tailored to specific phenotypes, and facilitating collaborative translation of science into diagnostics, devices, and therapeutics. Proposed priority actions outlined in the document include real-time measurement of biological changes preceding disease onset, more effective quantification of fibrosis, exploration of technologies for local treatment of fistulas, and the development of drug delivery platforms for precise, location-restricted therapies. Additionally, there is a strong emphasis on fostering collaboration between various stakeholders to accelerate progress in IBD research and treatment. Addressing these research gaps necessitates the exploration and implementation of bio-engineered novel technologies spanning a spectrum from materials to systems. By harnessing innovative ideas and technologies, there's a collective effort to enhance patient care and outcomes for individuals affected by IBD.

Challenges in IBD Research 2024: Precision Medicine.

Precision medicine is part of 5 focus areas of the Challenges in IBD Research 2024 research document, which also includes preclinical human IBD mechanisms, environmental triggers, novel technologies, and pragmatic clinical research. Building on Challenges in IBD Research 2019, the current Challenges aims to provide a comprehensive overview of current gaps in inflammatory bowel diseases (IBDs) research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient-centric research prioritization. In particular, the precision medicine section is focused on the main research gaps in elucidating how to bring the best care to the individual patient in IBD. Research gaps were identified in biomarker discovery and validation for predicting disease progression and choosing the most appropriate treatment for each patient. Other gaps were identified in making the best use of existing patient biosamples and clinical data, developing new technologies to analyze large datasets, and overcoming regulatory and payer hurdles to enable clinical use of biomarkers. To address these gaps, the Workgroup suggests focusing on thoroughly validating existing candidate biomarkers, using best-in-class data generation and analysis tools, and establishing cross-disciplinary teams to tackle regulatory hurdles as early as possible. Altogether, the precision medicine group recognizes the importance of bringing basic scientific biomarker discovery and translating it into the clinic to help improve the lives of IBD patients.

Challenges in IBD Research 2024: Preclinical Human IBD Mechanisms.

Preclinical human inflammatory bowel disease (IBD) mechanisms is one of 5 focus areas of the Challenges in IBD Research 2024 document, which also includes environmental triggers, novel technologies, precision medicine, and pragmatic clinical research. Herein, we provide a comprehensive overview of current gaps in inflammatory bowel diseases research that relate to preclinical research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in IBD interception, remission, and restoration. The document is the result of multidisciplinary input from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization. This preclinical human IBD mechanisms section identifies major research gaps whose investigation will elucidate pathways and mechanisms that can be targeted to address unmet medical needs in IBD. Research gaps were identified in the following areas: genetics, risk alleles, and epigenetics; the microbiome; cell states and interactions; barrier function; IBD complications (specifically fibrosis and stricturing); and extraintestinal manifestations. To address these gaps, we share specific opportunities for investigation for basic and translational scientists and identify priority actions.

Challenges in IBD Research 2024: Pragmatic Clinical Research.

Pragmatic clinical research is 1 of the 5 focus areas of the Challenges in IBD Research 2024, a multidisciplinary effort by scientists, clinicians, patients, and funders to identify priorities for patient-centric research. This summary provides a comprehensive overview of current gaps in inflammatory bowel disease (IBD) clinical research and actionable approaches to address them. This review is focused on identifying research that is needed to achieve the best outcomes for patients in clinical practice. Research gaps include understanding the needs of understudied patient groups and addressing barriers to care so all patients receive optimal care, validating and using biomarkers to enable early diagnosis and result in better outcomes for adults and children with IBD, and determining the optimal sequencing of treatments (medical, surgical, adjunct) in children and adults. Inclusive pragmatic research is needed to address these gaps and lead to improvements in patient care and outcomes for all populations of patients with IBD.

Research progress of ferroptosis and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a non-specific chronic inflammatory disorder of the gastrointestinal tract, imposing significant burdens on both society and individuals. As a new type of regulated cell death (RCD), ferroptosis is different from classic RCDs such as apoptosis and necrosis in cell morphology, biochemistry and genetics. The main molecular mechanisms of ferroptosis include dysregulation of iron metabolism, impaired antioxidant capacity, mitochondrial dysfunction, accumulation of lipid-associated super-oxides, and membrane disruption. In recent years, increasing evidence has shown that ferroptosis is involved in the pathophysiology of inflammatory bowel disease. However, the exact roles and underlying molecular mechanisms have not been fully elucidated. This article reviews the mechanism of ferroptosis in the occurrence and development of inflammatory bowel disease, in order to provide new ideas for the pathophysiological research of inflammatory bowel disease. Additionally, we discuss potential strategies for the prevention and treatment of inflammatory bowel disease by targeting ferroptosis.

The Role of Gut Microbiota in Inflammatory Bowel Disease: Mechanisms and Therapeutic Opportunities

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is characterized by chronic inflammation within the gastrointestinal tract. Emerging research underscores the pivotal role of alterations in gut microbiota composition and function in driving IBD pathogenesis. This paper offers a comprehensive overview of the intricate mechanisms governing the interplay between the gut microbiota and the host immune system, elucidating their contribution to IBD development and progression. Furthermore, we provide in-depth analysis and synthesis of the therapeutic opportunities presented by targeting the gut microbiota for IBD management. Specifically, we explore the application of probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and microbial-based therapies in the field of IBD studies. Each therapeutic modality is examined for its potential in modulating the gut microbiota and restoring microbial balance, thereby alleviating inflammation and ameliorating IBD symptoms. By elucidating these therapeutic opportunities and their applications in IBD research, this review not only enhances our understanding of IBD pathophysiology but also informs the development of innovative treatment strategies aimed at improving patient outcomes and enhancing quality of life.

Epidemiological research, burden, and clinical advances of inflammatory bowel disease in China.

Epidemiological research, burden, and clinical advances of inflammatory bowel disease in China.

Patient and public involvementin the development of health services: Engagement of underserved populations in a quality improvement programme for inflammatory bowel disease using a community-based participatory approach.

Involving people with lived experience is fundamental to healthcare development and delivery. This is especially true for inflammatory bowel disease (IBD) services, where holistic and personalised models of care are becoming increasingly important. There is, however, a significant lack of representation of underserved and diverse groups in IBD research, and there are significant barriers to healthcare access and utilisation among minority groups in IBD. IBD centres need to be aware of these experiences to address barriers via service changes, improve interactions with local communities and promote meaningful engagement for improved health outcomes. A pragmatic community-based approach was taken to engage with leaders and members of underserved groups across 11 workshops representing Roma, Afro-Caribbean, people of African descent and the wider black, Asian and minority ethnic (BAME) communities, Muslim women, refugee community members, deprived areas of South Yorkshire, LGBTQ+ and deaf populations. Thematic analysis of field notes identified patterns of attention across the community groups and where improvements to services were most frequently suggested. Findings demonstrated several barriers experienced to healthcare access and utilisation, including language accessibility, staff attitudes and awareness, mental health and stigma, continuity of support, and practical factors such as ease of service use and safe spaces. These barriers acted as a lever to co-producing service changes that are responsive to the health and social care needs of these groups. Engaging with people from a range of communities is imperative for ensuring that service improvements in IBD are accessible and representative of individual needs and values. Local community leaders and members of community groups actively participated in the co-design and development of improvements to the IBDservice for a local hospital. Their contributions further informed a pilot process for quality improvement programmes in IBD centres.

The Application of Intestinal Stem Cell Organoids in the Treatment of Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD) comprises chronic inflammatory disorders affecting the gastrointestinal tract, such as Crohn’s Disease (CD) and Ulcerative Colitis (UC). The escalating global incidence of IBD is multifactorial, involving genetic, microbial, environmental and immunological factors. Despite current therapies emphasizing immune suppression, sustained efficacy remains elusive. Recently, Stem Cell Therapy (SCT) has emerged as a potential avenue for inducing remission in IBD patients. Intestinal Stem Cells (ISCs) have gained attention for their recent emergence in research and potential cultivation into organoids, offering a promising source for IBD treatment. This review focuses on the potential of ISC SCT, emphasizing its organoid culturing capabilities. It highlights organoids’ applications in IBD research, monitors advancements in animal and human trials and examines current limitations and future directions in organoid research for IBD treatment.

Catalyzing change: Implementing standardised reporting in monogenic inflammatory bowel disease research.

Catalyzing change: Implementing standardised reporting in monogenic inflammatory bowel disease research.

An in vitro model to study immune activation, epithelial disruption and stromal remodelling in inflammatory bowel disease and fistulising Crohn's disease.

At present, preclinical models of inflammatory bowel disease (IBD) are insufficient, limiting translation between research and new therapeutics. This is especially true for fistulising Crohn's disease (CD), as the severe lack of relevant models hinders research progression. To address this, we present in vitro human IBD mucosal models that recapitulate multiple pathological hallmarks of IBD simultaneously in one model system - immune cell infiltration, stromal remodelling and epithelial disruption. Stimulation of models induces epithelial aberrations common in IBD tissue including altered morphology, microvilli abnormalities, claudin gene expression changes and increased permeability. Inflammatory biomarkers are also significantly increased including cytokines and chemokines integral to IBD pathogenesis. Evidence of extracellular matrix remodelling, including upregulated matrix-metalloproteinases and altered basement membrane components, suggests the models simulate pathological stromal remodelling events that closely resemble fistulising CD. Importantly, MMP-9 is the most abundant MMP and mimics the unique localisation observed in IBD tissue. The inflamed models were subsequently used to elucidate the involvement of TNF-α and IFN- γ in intestinal stromal remodelling, in which TNF-α but not IFN- γ induced MMP upregulation, specifically of MMP-3 and MMP-9. Collectively, our results demonstrate the potential of the IBD models for use in preclinical research in IBD, particularly for fistulising CD.

Changes in HLA-B27 Transgenic Rat Fecal Microbiota Following Tofacitinib Treatment and Ileocecal Resection Surgery: Implications for Crohn's Disease Management.

The therapeutic management of Crohn's disease (CD), a chronic relapsing-remitting inflammatory bowel disease (IBD), is highly challenging. Surgical resection is sometimes a necessary procedure even though it is often associated with postoperative recurrences (PORs). Tofacitinib, an orally active small molecule Janus kinase inhibitor, is an anti-inflammatory drug meant to limit PORs in CD. Whereas bidirectional interactions between the gut microbiota and the relevant IBD drug are crucial, little is known about the impact of tofacitinib on the gut microbiota. The HLA-B27 transgenic rat is a good preclinical model used in IBD research, including for PORs after ileocecal resection (ICR). In the present study, we used shotgun metagenomics to first delineate the baseline composition and determinants of the fecal microbiome of HLA-B27 rats and then to evaluate the distinct impact of either tofacitinib treatment, ileocecal resection or the cumulative effect of both interventions on the gut microbiota in these HLA-B27 rats. The results confirmed that the microbiome of the HLA-B27 rats was fairly different from their wild-type littermates. We demonstrated here that oral treatment with tofacitinib does not affect the gut microbial composition of HLA-B27 rats. Of note, we showed that ICR induced an intense loss of bacterial diversity together with dramatic changes in taxa relative abundances. However, the oral treatment with tofacitinib neither modified the alpha-diversity nor exacerbated significant modifications in bacterial taxa induced by ICR. Collectively, these preclinical data are rather favorable for the use of tofacitinib in combination with ICR to address Crohn's disease management when considering microbiota.

Early Initiation of Biologics and Disease Outcomes in Adults and Children With Inflammatory Bowel Diseases: Results From the Epidemiology Group of the Nationwide Israeli Inflammatory Bowel Disease Research Nucleus Cohort

In this nationwide study, we explored whether early initiation of biologics is associated with improved outcomes in children and adults with Crohn's disease (CD) and ulcerative colitis (UC). All patients diagnosed with CD or UC in Israel (2005-2020) were included in the Epidemiology Group of the Israeli Inflammatory Bowel Disease Research Nucleus cohort, encompassing 98% of the population. We compared disease duration at biologics initiation (ie, 0-3 months, >3-12 months, >1-2 years, and >2-3 years) using the cloning, censoring, and weighting by inverse probabilities method to emulate a target trial, adjusting for time-varying confounders and selection bias. Of the 34,375 included patients (of whom 5240 [15%] were children), 7452 of 19,264 (39%) with CD and 2235 of 15,111 (15%) with UC received biologics. In CD, by 10 years postdiagnosis, the probability of CD-related surgery decreased gradually but modestly with earlier initiation of biologics; a significant difference was noted between >2-3 years (31%) and 0-3 months (18%; P= .02; number needed to treat, 7.7), whereas there was no difference between the 0-3-month and >3-12-month periods. The 10-year probability of steroid dependency for the 0-3-month period (19%) differed both from the >2-3-year (31%; P < .001) and 1-2-year periods (37%; P < .001). In UC, no significant differences in colectomy or steroid dependency rates were observed between the treatment initiation periods. Similar trends were noted in the pediatric population. Very early initiation of biologics was not associated with some outcomes except for a modest risk reduction of surgery and steroid dependency for CD, which requires confirmation in future studies. In UC, early introduction of biologics was not associated with reduced risk of colectomy or steroid dependency.

Unveiling Colitis: A Journey through the Dextran Sodium Sulfate-induced Model.

Animal models of inflammatory bowel disease (IBD) are valuable tools for investigating the factors involved in IBD pathogenesis and evaluating new therapeutic options. The dextran sodium sulfate (DSS)-induced model of colitis is arguably the most widely used animal model for studying the pathogenesis of and potential treatments for ulcerative colitis (UC), which is a primary form of IBD. This model offers several advantages as a research tool: it is highly reproducible, relatively easy to generate and maintain, and mimics many critical features of human IBD. Recently, it has also been used to study the role of gut microbiota in the development and progression of IBD and to investigate the effects of other factors, such as diet and genetics, on colitis severity. However, although DSS-induced colitis is the most popular and flexible model for preclinical IBD research, it is not an exact replica of human colitis, and some results obtained from this model cannot be directly applied to humans. This review aims to comprehensively discuss different factors that may be involved in the pathogenesis of DSS-induced colitis and the issues that should be considered when using this model for translational purposes.

P814 Empowering IBD communities worldwide: The global impact of www.ibd-eii.com in disseminating evidence-based information and educational support

Abstract Background In recent decades, the volume of inflammatory bowel disease (IBD) research has surged, presenting a challenge for health care professionals to be updated. This is even more complicated for professionals in countries with low IBD prevalence and for registrars, fellows and other healthcare professionals. Methods IBD-EII website was launched the 8th February 2023 and serves as a comprehensive, unfunded and free platform offering up-to-date IBD evidence-based data. To highlight the impact, analyzing its first 8 months (data extracted via Google Analytics as of October 26, 2023) and using a google form questionnaire that was sent to subscribers in August 2023. Results The website encompasses over 300 trials and study summaries, along with 22 evidence-corner summaries, 102 guidelines from 12 scientific societies, 19 infographics featuring classifications and scores, 65 Cochrane meta-analyses and 13 network meta-analysis. Over the study period, there were 151,736 visits from 139 countries, with an average of 8.29 visits per user. The top-engaged countries were the United States, United Kingdom, Spain, Russia, and India (Figure 1). The site garnered 1058 subscriptions, with 10 (0.9%) individuals unsubscribing during the study period. Of the 850 invited users, 81 (9.5%) filled the questionnaire. Of them 53 (65.4%) were female. There were 49 (60.5%) healthcare professionals, 35 (43.2%) patients/family members of a patient, 4 (6%) were IBD researchers/ pharma industry workers, working for patients organization or both doctor and patient. Among healthcare professionals, 22 (44%) were IBD specialists, 14 (28%) general gastroenterologists, 4 (8%) trainees/ med school, 12 (24%) were IBD nurses/dieticians or pharmacists, 3 (6%) others. Most people have heard of the website in social media 66 (81.5%), by colleagues recommendation 8 (9.9%), congresses 7 (8.6%), or other 5 (6%). Website impact: 80 (98.8%) thought it was useful, 80 (98.8%) recommended to be subscribed. The most valuable sections were "evidence corner" 56 (69.1%) followed by guidelines 48 (59.3%) and timeline 35 (43.2%). Conclusion The data highlights the significant global impact of www.ibd-eii.com in disseminating evidence-based information to a diverse international community of healthcare professionals and patients. The website stands as a novel resource, fostering collaboration and empowerment within the global IBD community.

P089 Development and preliminary evaluation of a suicidal risk assessment protocol in a research trial using the Patient Health Questionnaire (PHQ-9)

Abstract Background People with Inflammatory Bowel Disease (IBD) have an increased risk of depression and self-harm. Participants in IBD research trials often disclose severe depression symptoms, including thoughts of self-harm and suicidal ideation, in validated self-administered questionnaires such as the Patient Health Questionnaire-9 (PHQ-9). However, there is no standard protocol for responding to such disclosure in research trials and the opportunity to support people at risk is potentially missed. We developed and evaluated a risk assessment protocol for the IBD-BOOST randomised controlled trial (ISRCTN71618461). Methods Participants completed the PHQ-9 scale at baseline, six-month and 12-month follow-up. Responding to item 9: ‘Thoughts that you would be better off dead or of hurting yourself in some way’, if a participant indicated ‘More than half the days’ or ‘Nearly every day’, the trial database automatically alerted the research team to risk assess the participant. Trial risk assessors, trained in the protocol, contacted participants by telephone, completed the risk assessment protocol (Figure 1) and signposted participants to appropriate professional services. Risk assessments were completed at the first occurrence of a PHQ-9 item 9 response. Risk assessments were reviewed by the Chief Investigator and summarised to trial governing committees. Results 780 participants were randomised. Overall, there were 58 PHQ-9 risk alerts during the trial (baseline, six- or 12-month follow-up), 41 of which were new alerts and required risk assessment. One participant declined assessment so 40 risk assessments were completed. 24 participants were assessed as low-risk and 16 participants as medium-risk, with 12 declaring previous suicide attempts. No participants were rated as high-risk. The mean time for the risk assessment phone call was 14 minutes (range 5-36 minutes) and total time spent on calls was approximately nine hours. Trial participants who received a risk assessment expressed appreciation for being contacted and all except two wished to receive information about professional support services. In a focus group, trial risk assessors reported positive experiences of conducting the risk assessment with suggestions for improvement, which resulted in minor modifications to the protocol. Conclusion Our evaluation demonstrated that it was viable for a research trial team to successfully conduct a risk-assessment protocol for trial participants reporting thoughts of self-harm, with training and support from senior colleagues. Resources are required for training and delivery, but it is not unduly onerous. Trial participants appeared to find completing the assessment acceptable. The revised protocol will be made available for researchers to use.

P1116 Risk of fractures in children and adults with inflammatory bowel disease: A report from the epi-IIRN

Abstract Background Both adult and pediatric patients with inflammatory bowel disease (IBD) are at risk of osteopenia and osteoporosis, nevertheless, whether patients with IBD are subjected to a higher risk for bone fractures is debated. Thus, we aimed to assess the risk for bone fractures, osteopenia and osteoporosis in IBD vs non-IBD patients, using the epi-Israeli IBD Research Nucleus (IIRN) data. Methods Data of patients with IBD and non-IBD matched controls (approximately 3 non-IBD controls per case) were retrieved from the epi-IIRN cohort (January 2005- June 2020) that maintain data on all patients with IBD from the four Israeli HMOs. Data included demographics, osteoporosis medications, fracture data and IBD related characteristics. Patients were stratified by age group (0-17,18-49, and ≥50). Patients with known osteopenia or osteoporosis before IBD diagnosis were excluded. Results We included 32,263 patients with IBD and 89,423 non-IBD controls [48% female, 56% Crohn’s disease (CD)]. Time to first fracture was significantly shorter in female pediatric patients (p=0.01), in both female (p=0.0004) and male (p=0.003) adult and elderly patients (p&amp;lt;0.0001) (Figure 1). Time to diagnosis of osteopenia/osteoporosis in patients with IBD was significantly shorter in all age groups and genders. Rate of fractures was significantly higher in patients with IBD versus controls for all groups, and rate of osteopenia/osteoporosis was also higher in patients with IBD in all groups (Table 1). In a subgroup analysis, fracture rate did not significantly differ between CD and ulcerative colitis (UC) for all age groups, but osteopenia and osteoporosis were significantly higher in CD compared to UC in all age groups. The hazard ratio for fractures in the pediatric IBD population was 1.02 (0.88-1.16) for males and 1.17(0.95-1.44) for females, in adults 1.08 (0.99-1.16) for males and 1.12 (1.02-1.21) for females, and in the elderly 1.2 (1.08-1.32) for males and 1.19 (1.08-1.31) for females. Arthritis was significantly associated with fracture risk [HR: children 1.47 (1.15-1.88); adults 1.3 (1.17-1.44); elderly 1.19 (1.07-1.30)]. In adults and elderly, older age at diagnosis, chronic obstructive pulmonary disease, diabetes and long-term proton pump inhibitors usage were also associated with a significant increase in fracture risk. Conclusion In this large nationwide cohort, patients with IBD had significantly higher risk for bone fractures than matched controls in almost all age groups, with no difference between CD and UC. Additionally, the rate of osteopenia and osteoporosis was higher in patients with IBD, suggesting that further efforts need to be invested in bone health of this at-risk population.

P035 3D bioprinting of gelatin derivatives: towards novel small intestinal in vitro models

Abstract Background Despite significant progress achieved in the field of inflammatory bowel disease research, the precise cause of the disease has yet to be elucidated. Intestinal in vitro models can provide a fast and inexpensive alternative for in vivo studies. Nonetheless, many in vitro models lack the crypt or crypt-villus architecture as seen in the large and small intestine respectively and therefore fail to mimic the complexity of the gut. In this study, we aim to improve the physiology of small intestinal in vitro models by the development of hydrogels that mirror the villi and crypts of the digestive tract. Methods This study focused on the development of gelatin-methacryloyl-aminoethyl-methacrylate (gel-MA-AEMA)-, and gelatin-methacryloyl-norbornene (gel-MA-NB)-based biomaterial inks to fabricate 3D constructs, mimicking villi or a combination of villi and crypts, with digital light processing. The constructs were mechanically and morphologically evaluated with parallel plate rheology and cryo-scanning electron microscopy respectively. To assess the biocompatibility of the 3D constructs, a Caco-2/HT29-MTX co-culture in a 9:1 ratio was maintained for 21 days and confluency was confirmed with immunofluorescence. Gene expression, transepithelial electrical resistance (TEER) and paracellular permeability of the cells cultured on the constructs were compared to cells cultured on flat gel-MA-AEMA and gel-MA-NB hydrogels, a collagen type I coating or uncoated tissue culture plastic. Results Both gel-MA-AEMA and gel-MA-NB hydrogels exhibited physiologically relevant stiffness (1.9 ± 0.63 kPa and 1.64 ± 0.63 kPa respectively), but only the gel-MA-AEMA based biomaterial ink could be successfully utilized for printing constructs with villi and crypts. On all construct designs, confluency was reached and paracellular permeability of small sized marker molecules in combination with TEER measurements suggested the formation of a functional barrier over time, which was further confirmed by immunofluorescence and increased gene expression of tight junction proteins, occludin and ZO-1. The gene expression of enterocyte differentiation markers, villin-1, sucrase isomaltase and alkaline phosphatase, suggested the superior differentiation of Caco-2 cells on the ‘only villi’ and ‘villi and crypts’ constructs compared to flat hydrogels, collagen type I coating or uncoated tissue culture plastic. Conclusion Although both hydrogels promoted functional barrier formation and enterocyte differentiation, gel-MA-AEMA was more suited for DLP than gel-MA-NB. In addition, culturing intestinal epithelial cells on the 3D constructs ameliorated cell differentiation compared to conventional 2D setups.

Animal models of inflammatory bowel disease: category and evaluation indexes.

Inflammatory bowel disease (IBD) research often relies on animal models to study the etiology, pathophysiology, and management of IBD. Among these models, rats and mice are frequently employed due to their practicality and genetic manipulability. However, for studies aiming to closely mimic human pathology, non-human primates such as monkeys and dogs offer valuable physiological parallels. Guinea pigs, while less commonly used, present unique advantages for investigating the intricate interplay between neurological and immunological factors in IBD. Additionally, New Zealand rabbits excel in endoscopic biopsy techniques, providing insights into mucosal inflammation and healing processes. Pigs, with their physiological similarities to humans, serve as ideal models for exploring the complex relationships between nutrition, metabolism, and immunity in IBD. Beyond mammals, non-mammalian organisms including zebrafish, Drosophila melanogaster, and nematodes offer specialized insights into specific aspects of IBD pathology, highlighting the diverse array of model systems available for advancing our understanding of this multifaceted disease. In this review, we conduct a thorough analysis of various animal models employed in IBD research, detailing their applications and essential experimental parameters. These include clinical observation, Disease Activity Index score, pathological assessment, intestinal barrier integrity, fibrosis, inflammatory markers, intestinal microbiome, and other critical parameters that are crucial for evaluating modeling success and drug efficacy in experimental mammalian studies. Overall, this review will serve as a valuable resource for researchers in the field of IBD, offering insights into the diverse array of animal models available and their respective applications in studying IBD.

Intestinal Membrane Function in Inflammatory Bowel Disease.

Inflammatory bowel disease is a set of chronic inflammatory diseases that mainly develop in the gastrointestinal mucosa, including ulcerative colitis and Crohn's disease. Gastrointestinal membrane permeability is an important factor influencing the pharmacological effects of pharmaceuticals administered orally for treating inflammatory bowel disease and other diseases. Understanding the presence or absence of changes in pharmacokinetic properties under a disease state facilitates effective pharmacotherapy. In this paper, we reviewed the gastrointestinal membrane function in ulcerative colitis and Crohn's disease from the perspective of in vitro membrane permeability and electrophysiological parameters. Information on in vivo permeability in humans is summarized. We also overviewed the inflammatory bowel disease research using gut-on-a-chip, in which some advances have recently been achieved. It is expected that these findings will be exploited for the development of therapeutic drugs for inflammatory bowel disease and the optimization of treatment options and regimens.