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

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

Deadline for manuscript submissions: closed (31 August 2025) | Viewed by 11168

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Dr. Dingpei Long

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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
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Dr. Junsik Sung

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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

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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 (11 papers)

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17 pages, 826 KB

Open AccessArticle

Immunological Linkages Between Inflammatory Bowel Diseases and Type 2 Diabetes

by Davide Frumento and Ștefan Țălu

Biomedicines 2025, 13(9), 2224; https://doi.org/10.3390/biomedicines13092224 - 10 Sep 2025

Viewed by 149

Abstract

Background: Inflammatory bowel disease (IBDs) are chronic, immune-mediated disorders of the gastrointestinal tract, encompassing ulcerative colitis (UC) and Crohn’s disease (CD), and primarily affecting individuals with genetic susceptibility. IBDs are characterized by dysregulated mucosal immune responses to intestinal microbiota, leading to sustained inflammation and tissue damage. These conditions not only pose a significant burden on healthcare systems but are also frequently associated with distinct comorbidities. Rationale: Given the immunological nature of both IBDs and type 2 diabetes (T2D)—each involving a complex interplay between genetic predisposition and environmental triggers—an increasing number of studies have suggested a pathophysiological link between the two. Both diseases involve chronic low-grade inflammation and alterations in immune signaling pathways, such as cytokine dysregulation, T-cell imbalance, and aberrant innate immune activation. Methods: To investigate this association more robustly, we conducted a cohort study involving 49 consecutive patients diagnosed with both IBD and T2D. Results: Our findings revealed a strong correlation between the two conditions, with UC emerging as the predominant IBD subtype linked to T2D. Notably, the highest prevalence was observed in patients aged 65–74 years, suggesting age-related immune modulation may play a role. In a matched case-control analysis (48 cases vs. 96 controls), 70.8% of the IBD–T2D cases were diagnosed with UC, 25.0% with CD, and 4.2% with indeterminate colitis. Similarly, in the cohort study, UC accounted for 73.81% of cases, CD for 21.43%, and non-determined colitis for 4.76%. Conclusions: These data support the hypothesis that UC, more so than CD, exhibits a stronger immunological and clinical association with T2D. Interestingly, CD was absent in the 55–64 age group, potentially indicating age-specific immunological trajectories or differential environmental exposures. The observed patterns reinforce the concept that immune dysregulation is a shared underpinning of both IBD and T2D, and that UC may serve as an immunological bridge linking gastrointestinal and metabolic inflammation. 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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14 pages, 762 KB

Open AccessArticle

COVID-19 and COVID-19 Vaccinations Lead to Serological Responses in Patients with Inflammatory Bowel Diseases Independent of the Type of Immunomodulatory Medication

by Larissa Kunoff, Martin Kreysing and Annika Gauss

Biomedicines 2025, 13(9), 2072; https://doi.org/10.3390/biomedicines13092072 - 26 Aug 2025

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Abstract

Background/Objectives: The COVID-19 pandemic and the development of vaccines provided the opportunity to monitor disease prevalence and outcomes, vaccinations, their side effects and serological responses in patients with inflammatory bowel disease (IBD). Methods: IBD patients of the outpatient clinic at the University Hospital Heidelberg who completed at least one questionnaire on COVID-19 and related vaccinations from July 2021 to August 2022 were included. Spike-IgG antibody titres were determined. Friedman tests, Wilcoxon signed-rank tests and Kruskal–Wallis tests were used for comparisons. The influence of IBD therapy was analysed using linear models with mixed effects. Results: The cohort included 520 patients (269 females, mean age = 45.3 years, 60.6% with Crohn’s disease, 35.4% with ulcerative colitis, and 4.0% with unclassified IBD). Four hundred eighty patients (92.3%) received at least one COVID-19 vaccination, and 154 patients (29.6%) were infected by SARS-CoV-2. Among all of them, 94.4% achieved seroconversion. Triple-vaccinated patients with additional SARS-CoV-2 infection developed the highest serological responses (χ² = 16.51, p < 0.001, df = 3). An antibody decay over time was observed after the second (p < 0.001) and third vaccinations (p < 0.001). Regarding individual IBD medications, no differences in mean titres were found after two (χ² = 6.60, p = 0.36, df = 6) versus three vaccinations (χ² = 4.97, p = 0.42, df = 5). Linear models with mixed effects revealed no influence of IBD therapies on serological responses. Conclusions: The highest serological responses were observed in IBD patients after three vaccinations plus SARS-CoV-2 infection without significant differences between IBD therapies. 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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11 pages, 682 KB

Open AccessArticle

Long-Term Outcomes of First-Line Anti-TNF Therapy for Chronic Inflammatory Pouch Conditions: A Multi-Centre Multi-National Study

by Itai Ghersin, Maya Fischman, Giacomo Calini, Eduard Koifman, Valerio Celentano, Jonathan P. Segal, Orestis Argyriou, Simon D. McLaughlin, Heather Johnson, Matteo Rottoli, Kapil Sahnan, Janindra Warusavitarne and Ailsa L. Hart

Biomedicines 2025, 13(8), 1870; https://doi.org/10.3390/biomedicines13081870 - 1 Aug 2025

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Abstract

Background/Objectives: Anti-tumour necrosis factor (anti-TNF) medications were historically commonly prescribed as the first-line biologic treatment for chronic inflammatory pouch conditions. However, their use in these conditions is mainly based on retrospective studies of relatively small numbers of patients with short follow up periods. We aimed to describe the long-term outcomes of first-line anti-TNF therapy in a large, multi-centre, multi-national patient cohort with chronic inflammatory pouch conditions. Methods: This was an observational, retrospective, multi-centre, multi-national study. We included patients with chronic inflammatory pouch conditions initially treated with anti-TNF drugs infliximab (IFX) or adalimumab (ADA), who had a follow up of at least 1 year. The primary outcome was anti-TNF treatment persistence, defined as continuation of anti-TNF throughout the study period. The secondary outcome was pouch failure, defined by the need for a defunctioning ileostomy or pouch excision. Results: We recruited 98 patients with chronic inflammatory pouch conditions initially treated with anti-TNF medications—63 (64.3%) treated with IFX and 35 (35.7%) treated with ADA. Average follow up length was 94.2 months (±54.5). At the end of the study period only 22/98 (22.4%) patients were still on anti-TNF treatment. In those in whom the first-line anti-TNF was discontinued, the median time to discontinuation was 12.2 months (range 5.1–26.9 months). The most common cause for anti-TNF discontinuation was lack of efficacy despite adequate serum drug levels and absence of anti-drug antibody formation (30 patients, 30.6%). Loss of response due to anti-drug antibody formation was the cause for discontinuation in 18 patients (18.4%), while 12 patients (12.2%) stopped treatment because of adverse events or safety concerns. Out of the 76 patients discontinuing anti-TNF treatment, 34 (34.7% of the cohort) developed pouch failure, and 42 (42.8% of the cohort) are currently treated with a different medical therapy. Conclusions: First-line anti-TNF therapy for chronic pouch inflammatory conditions is associated with low long-term persistence rates. This is due to a combination of lack of efficacy and adverse events. A significant percentage of patients initially treated with anti-TNF therapy develop pouch failure. 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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12 pages, 385 KB

Open AccessArticle

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

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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 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 KB

Open AccessArticle

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

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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 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 KB

Open AccessArticle

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 844

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 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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17 pages, 1495 KB

Open AccessReview

Risk for COVID-19 Vulnerability in Patients with Inflammatory Bowel Disease: Assessing Alterations in ACE2 and TMPRSS2

by Jorge Sáez-Leyva, Matthew P. Lennol, Carlos Avilés-Granados, María-Salud García-Ayllón and Javier Sáez-Valero

Biomedicines 2025, 13(9), 2240; https://doi.org/10.3390/biomedicines13092240 - 11 Sep 2025

Viewed by 181

Abstract

Chronic inflammatory conditions often involve the dysregulation of key enzymes, including serine proteases such as transmembrane serine protease 2 (TMPRSS2) and the angiotensin converting enzyme 2 (ACE2), which are key proteins implicated in the cellular entry mechanism of SARS-CoV-2. It remains uncertain whether the gastrointestinal symptoms observed in COVID-19 patients result from direct viral infection of the gastrointestinal tract, a process that may be exacerbated by altered expression of ACE2 or TMPRSS2. In this review, we explore the interplay among ACE2 and TMPRSS2 in the context of inflammatory bowel disease (IBD), including their roles in disease pathology and response to therapy. We also examine methodological approaches for assessing whether protease alterations contribute to increased susceptibility to infection, considering that TMPRSS2 exists in inactive (zymogen) and active forms. Furthermore, while membrane-bound ACE2 facilitates viral entry, soluble ACE2 fragments may act as decoys, preventing virus–receptor interaction. Therefore, the interpretation of changes in full-length versus cleaved forms of ACE2 and related enzymes is critical for understanding vulnerability to SARS-CoV-2 infection. 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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35 pages, 2034 KB

Open AccessReview

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 1447

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 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 KB

Open AccessReview

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 767

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 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, 659 KB

Open AccessReview

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 1908

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 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 KB

Open AccessReview

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 2183

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 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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