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Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic...
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Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition)

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 4841

Special Issue Editors

Dr. Dingpei Long

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Guest Editor
1. Digestive Disease Research Group, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
2. State Key Laboratory of Silkworm Genome Biology, Key Laboratory for Sericulture Functional Genomics & Biotechnology of Agricultural Ministry, Southwest University, Chongqing 400716, China
Interests: inflammatory bowel disease (IBD); ulcerative colitis (UC); colitis-associated cancer (CAC); drug delivery systems (DDSs); natural lipid nanoparticles; natural/genetically modified silk fibroin nanoparticles
Special Issues, Collections and Topics in MDPI journals
Dr. Junsik Sung

E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21250, USA
Interests: nanoparticles; nanomedicine; targeted drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Inflammatory bowel disease (IBD) is a group of chronic conditions affecting the digestive tract, with Crohn’s disease (CD) and ulcerative colitis (UC) being the two main forms. The exact cause of IBD is unknown, but a combination of genetic and environmental factors is believed to be involved. The disease is characterized by a range of symptoms, including abdominal pain, diarrhea, rectal bleeding, weight loss, and malnutrition. The pathophysiology of IBD involves an abnormal immune response in the gut, leading to chronic inflammation and damage to the intestinal lining. Treating IBD has been a challenge for the medical community due to the complexity of the disease and limited understanding of its pathophysiology. Current therapies include medications reducing inflammation, such as corticosteroids, immunosuppressants, and biologic therapies, but these can have significant side effects and may not be effective for all patients. Innovative therapeutic approaches for IBD, including stem cell transplantation, fecal microbiota transplantation, and modulation of the gut microbiome, are currently under investigation. Researchers are also exploring targeted therapies targeting the underlying causes of IBD, such as novel drug delivery platforms based on micro- and nanotechnology. Significant advances have been made in understanding the mechanisms of IBD and developing new therapeutic approaches in recent years. This Special Issue will publish the latest research advances in IBD and bring together researchers and clinical doctors participating in IBD research. Global experts will discuss topics such as the mechanisms of IBD and research advances in the prevention, diagnosis, and treatment of IBD.

Dr. Dingpei Long
Dr. Junsik Sung
Guest Editors

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Keywords

  • inflammatory bowel disease
  • Crohn’s disease
  • ulcerative colitis
  • chronic inflammation
  • pathophysiological mechanisms
  • therapeutic approaches
  • stem cell transplantation
  • fecal microbiota transplantation
  • gut microbiome
  • targeted therapies

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Published Papers (7 papers)

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Research

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12 pages, 385 KiB  
Article
Psychological Profiles in Ulcerative Colitis and Crohn’s Disease: Distinct Emotional and Behavioral Patterns
by Antonio Maria D’Onofrio, Eleonora Maggio, Valentina Milo, Gaspare Filippo Ferrajoli, Daniele Ferrarese, Daniela Pia Rosaria Chieffo, Massimiliano Luciani, Antonio Gasbarrini, Gabriele Sani, Franco Scaldaferri, Rosaria Calia and Giovanni Camardese
Biomedicines 2025, 13(7), 1694; https://doi.org/10.3390/biomedicines13071694 - 10 Jul 2025
Viewed by 400
Abstract
Background/Objectives: Ulcerative colitis (UC) and Crohn’s disease (CD) are two forms of inflammatory bowel disease (IBD), which, despite their shared inflammatory nature, differ markedly in clinical presentation and disease course. In this study, we aimed to explore whether these clinical differences are [...] Read more.
Background/Objectives: Ulcerative colitis (UC) and Crohn’s disease (CD) are two forms of inflammatory bowel disease (IBD), which, despite their shared inflammatory nature, differ markedly in clinical presentation and disease course. In this study, we aimed to explore whether these clinical differences are also reflected at the psychological level. Specifically, we sought to delineate the personality characteristics of a sample of patients with IBD and to investigate psychological and psychopathological differences between individuals with UC and CD. Methods: We enrolled 29 (44.61%) UC patients and 36 (55.39%) CD patients, all aged 18 years or older. Each participant completed the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), which was subsequently scored and interpreted by trained psychologists. The MMPI-2 is a 567-item inventory with dichotomous answers (true/false), providing measures of a wide range of symptoms, beliefs, attitudes, and personality traits. Results: The total sample showed clinically significant elevations on hypochondriasis (Hs), health concerns (HEA), general health concerns (HEA3), and physical malfunctioning (D3) scales. UC patients had statistically significant higher scores on hypomania (p = 0.043), lack of ego mastery—defective inhibition (p = 0.006), and fears (p = 0.038) scales than CD patients. On the other hand, CD patients showed statistically significant higher scores on the Overcontrolled Hostility scale (p = 0.043). Conclusions: Both groups of patients experience emotional difficulties related to their clinical conditions, leading to an increased preoccupation with bodily symptoms and illness. These aspects appear to be accompanied by shifts in mood towards a more depressive state. Notably, the UC group demonstrates a greater degree of impairment compared to the CD group, with experiences of anxiety, stress, difficulties in emotional control, and emerging relational challenges. Full article
(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))
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18 pages, 569 KiB  
Article
Impact of Biologics and Proton Pump Inhibitors on Gastrointestinal Infection Risk in Inflammatory Bowel Disease Patients: A Retrospective Analysis of Pathogen-Specific Outcomes and Treatment Interactions
by Ryan Njeim, Elie Moussa, Chapman Wei, Joelle Sleiman, Reem Dimachkie and Liliane Deeb
Biomedicines 2025, 13(7), 1676; https://doi.org/10.3390/biomedicines13071676 - 8 Jul 2025
Viewed by 372
Abstract
Background/Objectives: Inflammatory bowel disease (IBD) patients face elevated gastrointestinal (GI) infection risks due to immune dysregulation and gut dysbiosis. While steroids and immunosuppressants are known to increase infection risk, data on biologics and proton pump inhibitors (PPIs) remain limited, particularly for non-Clostridioides [...] Read more.
Background/Objectives: Inflammatory bowel disease (IBD) patients face elevated gastrointestinal (GI) infection risks due to immune dysregulation and gut dysbiosis. While steroids and immunosuppressants are known to increase infection risk, data on biologics and proton pump inhibitors (PPIs) remain limited, particularly for non-Clostridioides difficile (C.diff) infections. Methods: This retrospective cohort study analyzed 9849 hospitalized IBD patients (2013–2023) from the Northwell Inpatient Database. Patients were categorized into four groups: biologics-only, PPIs-only, both, or neither. GI infections were identified via C.diff PCR, GI PCR, and chart review. Multivariate logistic regression adjusted for demographics, BMI, and IBD type. Results: GI infections occurred in 1.75% of patients, with significantly higher odds in those on biologics alone (OR 21.5, 95% CI 11.7–39.4) or with PPIs (OR 16.6, 95% CI 10.2–26.8) versus untreated patients. Non-C.diff infections were strongly associated with biologics (OR 20.7, 95% CI 10.2–41.9). PPIs alone increased slightly the risk of GI infections (OR 1.6, 95% CI 1.1–2.4). Vedolizumab and adalimumab had the highest infection risks among biologics (26.8% and 22.7%, respectively). Bacterial pathogens, such as E. coli and Salmonella, predominated, with no significant difference in causative agents across treatment groups. Conclusions: Biologic therapy greatly increases GI infection risk in IBD patients independent of PPI use. Clinicians should weigh infection risks when prescribing biologics, particularly in high-risk populations. Further studies are needed to assess risks by biologic subtype and the interplay with PPIs. Full article
(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))
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15 pages, 3116 KiB  
Article
Integrated Single-Cell Transcriptome Analysis Reveals Novel Insights into the Role of Opioid Signaling in the Pathophysiology of Inflammatory Bowel Disease
by Mudan Zhang, Zhuo Xie, Shenghong Zhang and Gaoshi Zhou
Biomedicines 2025, 13(6), 1398; https://doi.org/10.3390/biomedicines13061398 - 6 Jun 2025
Viewed by 586
Abstract
Background/Objectives: Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic gastrointestinal inflammatory diseases with complex etiology and remains a therapeutic challenge due to heterogeneous treatment responses. Opioids are widely used for analgesic management in IBD, yet [...] Read more.
Background/Objectives: Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic gastrointestinal inflammatory diseases with complex etiology and remains a therapeutic challenge due to heterogeneous treatment responses. Opioids are widely used for analgesic management in IBD, yet the role of opioid signaling in IBD remains unclear. Methods: We employed single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing, CellChat analysis, and transcription factor activity assessment to systematically investigate the roles and underlying mechanisms of opioid signaling-related genes in IBD. Results: We characterized opioid signaling-related genes in IBD at single-cell resolution and identified a novel subset of monocytes with a high expression level of opioid signaling-related genes (OpiHi monocytes). OpiHi monocytes were enriched in IBD tissues and served as a predominant source of tumor necrosis factor (TNF)-related signaling in the tissues of IBD. An inflammatory microenvironment in IBD drove the generation of OpiHi monocytes. Moreover, the prediction model based on OpiHi monocytes marker genes had robust predictive performance for the therapeutic response to anti-TNF therapy in IBD. Conclusions: This study provides novel insights into opioid signaling in IBD pathogenesis at the cellular level and establishes a reliable biomarker for precise management of anti-TNF therapy. Full article
(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))
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Review

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35 pages, 2034 KiB  
Review
The Role of Gut Microbiota in Gastrointestinal Immune Homeostasis and Inflammation: Implications for Inflammatory Bowel Disease
by Elisabetta Bretto, Miquel Urpì-Ferreruela, Gherzon Rimer Casanova and Begoña González-Suárez
Biomedicines 2025, 13(8), 1807; https://doi.org/10.3390/biomedicines13081807 - 24 Jul 2025
Viewed by 435
Abstract
Inflammatory bowel disease (IBD), a heterogeneous group of recurring inflammatory conditions of the digestive system that encompass both ulcerative colitis (UC) and Crohn’s disease (CD), pose a significant public health challenge, currently lacking a definitive cure. The specific etiopathogenesis of IBD is not [...] Read more.
Inflammatory bowel disease (IBD), a heterogeneous group of recurring inflammatory conditions of the digestive system that encompass both ulcerative colitis (UC) and Crohn’s disease (CD), pose a significant public health challenge, currently lacking a definitive cure. The specific etiopathogenesis of IBD is not yet fully understood, but a multifactorial interplay of genetic and environmental factors is suspected. A growing body of evidence supports the involvement of intestinal dysbiosis in the development of IBD, including the effects of dysbiosis on the integrity of the intestinal epithelial barrier, modulation of the host immune system, alterations in the enteric nervous system, and the perpetuation of chronic inflammation. A comprehensive understanding of these mechanisms is important to define preventive measures, to develop new effective and lasting treatments, and to improve disease outcome. This review examines the complex tri-directional relationship between gut microbiota, mucosal immune system, and intestinal epithelium in IBD. In addition, nonpharmacological and behavioral strategies aimed at restoring a proper microbial–immune relationship will be suggested. Full article
(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))
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17 pages, 659 KiB  
Review
Insights into the Molecular Mechanisms and Novel Therapeutic Strategies of Stenosis Fibrosis in Crohn’s Disease
by Yuan Zhou, Huiping Chen, Qinbo Wang, Guozeng Ye, Yingjuan Ou, Lihong Huang, Xia Wu and Jiaxi Fei
Biomedicines 2025, 13(7), 1777; https://doi.org/10.3390/biomedicines13071777 - 21 Jul 2025
Viewed by 310
Abstract
Crohn’s disease (CD), characterized by chronic gastrointestinal inflammation, is complicated by intestinal stenosis resulting from dysregulated fibrogenesis and is marked by excessive extracellular matrix (ECM) deposition, fibroblast activation, and luminal obstruction. While biologics control inflammation, their failure to halt fibrosis underscores a critical [...] Read more.
Crohn’s disease (CD), characterized by chronic gastrointestinal inflammation, is complicated by intestinal stenosis resulting from dysregulated fibrogenesis and is marked by excessive extracellular matrix (ECM) deposition, fibroblast activation, and luminal obstruction. While biologics control inflammation, their failure to halt fibrosis underscores a critical therapeutic void. Emerging evidence highlights the multifactorial nature of stenosis-associated fibrosis, driven by profibrotic mediators and dysregulated crosstalk among immune, epithelial, and mesenchymal cells. Key pathways, including transforming growth factor (TGF-β), drosophila mothers against decapentaplegic protein (Smad) signaling, Wnt/β-catenin activation, epithelial–mesenchymal transition (EMT), and matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP)-mediated ECM remodeling, orchestrate fibrotic progression. Despite the current pharmacological, endoscopic, and surgical interventions for fibrostenotic CD, their palliative nature and inability to reverse fibrosis highlight an unmet need for disease-modifying therapies. This review synthesizes mechanistic insights, critiques therapeutic limitations with original perspectives, and proposes a translational roadmap prioritizing biomarker-driven stratification, combinatorial biologics, and mechanistically targeted antifibrotics. Full article
(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))
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22 pages, 643 KiB  
Review
JAK Inhibitor and Crohn’s Disease
by Mengyan Xu, Shi Wang, Sanping Xu and Rui Gong
Biomedicines 2025, 13(6), 1325; https://doi.org/10.3390/biomedicines13061325 - 29 May 2025
Viewed by 870
Abstract
Crohn’s disease is a chronic inflammatory granulomatous disease of the gastrointestinal tract. The global incidence and prevalence of Crohn’s disease have significantly increased, largely due to genetic susceptibility, environmental changes, and advancements in diagnostic technology. In recent years, the pharmacologic treatment of Crohn’s [...] Read more.
Crohn’s disease is a chronic inflammatory granulomatous disease of the gastrointestinal tract. The global incidence and prevalence of Crohn’s disease have significantly increased, largely due to genetic susceptibility, environmental changes, and advancements in diagnostic technology. In recent years, the pharmacologic treatment of Crohn’s disease has been rapidly changing, and although biologics have improved the prognosis of patients to a certain extent, they still have certain limitations. Oral small molecule drugs like JAK inhibitors have become a research hotspot because of their advantages of targeting and regulating the JAK/STAT pathway, convenient administration, and rapid onset of action. JAK inhibitors exhibit divergent therapeutic profiles. Clinical trials have shown that tofacitinib demonstrates limited efficacy in Crohn’s disease management. Filgotinib initially showed clinical remission in phase 2 trials; while its subsequent phase 3 studies failed to demonstrate consistent endoscopic improvement. In contrast, upadacitinib achieved notable clinical remission rates during both induction and maintenance phases of phase 2 trials. However, long-term safety concerns, including thromboembolic events, cardiovascular events, opportunistic infections, and potential malignancy risks, warrant cautious clinical application. This article systematically reviews the pathophysiology of Crohn’s disease, and the evidence for the efficacy and safety of JAK inhibitors to guide clinical practice and research. Full article
(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))
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25 pages, 2527 KiB  
Review
Optimizing Biologic Therapy for the Prevention of Post-Operative Recurrence in Crohn’s Disease: Current Evidence and Future Perspectives
by Reem Aljabri, Saqer Al-Saraie and Ahmed Alhouti
Biomedicines 2025, 13(5), 1232; https://doi.org/10.3390/biomedicines13051232 - 19 May 2025
Viewed by 1220
Abstract
Crohn’s disease (CD) imposes a substantial burden on patients due to its chronic, relapsing nature, often necessitating surgical intervention. However, surgery is not curative, and post-operative recurrence (POR) remains a major clinical challenge, with up to 80% of patients developing endoscopic recurrence within [...] Read more.
Crohn’s disease (CD) imposes a substantial burden on patients due to its chronic, relapsing nature, often necessitating surgical intervention. However, surgery is not curative, and post-operative recurrence (POR) remains a major clinical challenge, with up to 80% of patients developing endoscopic recurrence within one year if left untreated. The pathophysiology of POR is multifactorial, involving dysregulated immune responses, gut microbiota alterations, and mucosal healing impairment, highlighting the need for targeted therapeutic strategies. This review aims to explore the current landscape of POR management, focusing on biologic therapies and emerging advanced treatments. Conventional management relies on early prophylactic therapy with anti-TNF agents such as infliximab and adalimumab, which have demonstrated efficacy in reducing endoscopic and clinical recurrence. However, newer biologics, including IL-23 inhibitors (risankizumab) and Janus kinase (JAK) inhibitors (upadacitinib), have shown promise in CD management, though their role in POR remains underexplored. The lack of direct clinical evidence for advanced biologics in POR prevention, combined with inter-individual variability in treatment response, underscores the need for further research. Future directions should focus on optimizing therapeutic strategies through personalized medicine, identifying predictive biomarkers, and conducting robust trials to establish the efficacy of novel agents in POR prevention. A tailored, evidence-driven approach is essential to improving long-term outcomes and minimizing disease recurrence in post-operative CD patients. Full article
(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))
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