Integrating Genetics, Immune Dysregulation, and the Gut Microbiome: Advances in Elucidating IBD Pathophysiology and Emerging Therapeutic Strategies

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Genetics".

Deadline for manuscript submissions: 1 July 2025 | Viewed by 3569

Special Issue Editors


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Guest Editor
1. School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts & Sciences, ASU Mayo Health Futures Center, 6161 E. Mayo Blvd., Phoenix, AZ 85054, USA
2. Department of Basic Medical Sciences, College of Medicine, University of Arizona, Phoenix, AZ 85004, USA
Interests: GI disorders including IBD, IBS, colon cancer, and dysbiosis; role of nutraceuticals in health and disease; vitamin D and molecular mechanisms of nuclear receptors

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Guest Editor
School of Mathematical and Natural Sciences, New College of Interdisciplinary Arts & Sciences, Arizona State University West Valley Campus, 4701 W. Thunderbird Road, Glendale, AZ 85306, USA
Interests: molecular biosignatures; gut microbiome; rapid MALDI-TOF MS-based approaches to microbial characterization

Special Issue Information

Dear Colleagues,

Inflammatory bowel disease (IBD) consists of Crohn’s disease, ulcerative colitis, and indeterminate colitis. It is characterized by chronic inflammation of the gastrointestinal (GI) tract. It currently affects approximately 10 million people globally, and its incidence is increasing exponentially. The pathogenesis of IBD is incompletely understood, and well-defined diagnostic biomarkers and effective treatments are limited. Thus, further research is needed to ameliorate the IBD burden. Immune dysregulation, genetic susceptibility, and environmental triggers are suspected to be involved in the development of IBD, and multifactorial approaches that include both individual factors (exogenous and endogenous) and their interactions are likely necessary to further elucidate its pathophysiology. In this Special Issue, original research and review articles are welcome to be submitted as we explore biomarkers that might aid in the diagnosis, prediction of outcomes and responses, and treatment of IBD. In addition, works further exploring the roles of the microbiome, gut–brain axis, and environmental, immune, and genetic factors in IBD etiology will be presented. Given the multifactorial nature of IBD, articles that explore connections between different components of IBD pathophysiology, diagnosis, and treatment are particularly relevant to this Special Issue.

Prof. Dr. Peter W. Jurutka
Prof. Dr. Todd R. Sandrin
Guest Editors

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Keywords

  • microbiome
  • biomarkers
  • Crohn’s disease
  • ulcerative colitis
  • indeterminate colitis
  • multiomics
  • gastrointestinal (GI disease)
  • immunology
  • gut–brain axis
  • neuropsychology

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Published Papers (2 papers)

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Research

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19 pages, 6264 KiB  
Article
The Role of Claudins in the Pathogenesis of Dextran Sulfate Sodium-Induced Experimental Colitis: The Effects of Nobiletin
by Asmaa Al-Failakawi, Aishah Al-Jarallah, Muddanna Rao and Islam Khan
Biomolecules 2024, 14(9), 1122; https://doi.org/10.3390/biom14091122 - 4 Sep 2024
Cited by 1 | Viewed by 1416
Abstract
Background: The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic [...] Read more.
Background: The pathogenesis of inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease is not well understood. This study investigated the roles and regulation of the claudin-1, -2, -3, and -4 isoforms in the pathogenesis of ulcerative colitis, and the potential therapeutic effects of nobiletin. Methods: Colitis was induced in rats by administering dextran sulfate sodium [DSS] in drinking water for seven days. Animals were treated daily with nobiletin [oral, 60 mg/Kg body weight] and studied in four groups, C [non-colitis control], D [DSS-induced colitis], CN [nobiletin-treated non-colitis control], and DN [nobiletin-treated DSS-induced colitis]. On day seven, the animals were sacrificed, and colonic tissues were collected and analyzed. Results: Both macroscopic and microscopic findings suggest the progression of colitis. In the inflamed colon, claudin-1 and -4 proteins were decreased, claudin-2 increased, while the claudin-3 protein remained unchanged. Except for claudin-1, these changes were not paralleled by mRNA expression, indicating a complex regulatory mechanism. Uniform β-actin expression along with consistent quality and yield of total RNA indicated selectivity of these changes. Nobiletin treatment reversed these changes. Conclusions: Altered expression of the claudin isoforms -1, -2, and -4 disrupts tight junctions, exposing the lamina propria to microflora, leading to electrolyte disturbance and the development of ulcerative colitis. Nobiletin with its anti-inflammatory properties may be useful in IBD. Full article
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Review

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19 pages, 1149 KiB  
Review
Dual Therapy in Inflammatory Bowel Disease
by Gabriele Altieri, Alessandra Zilli, Tommaso Lorenzo Parigi, Mariangela Allocca, Federica Furfaro, Gionata Fiorino, Clelia Cicerone, Laurent Peyrin-Biroulet, Silvio Danese and Ferdinando D’Amico
Biomolecules 2025, 15(2), 222; https://doi.org/10.3390/biom15020222 - 3 Feb 2025
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Abstract
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic and complex autoimmune conditions. Despite the advancements in biologics and small molecules, the therapeutic ceiling persists, posing significant treatment challenges and contributing to the concept of difficult-to-treat IBD. Dual-targeted [...] Read more.
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic and complex autoimmune conditions. Despite the advancements in biologics and small molecules, the therapeutic ceiling persists, posing significant treatment challenges and contributing to the concept of difficult-to-treat IBD. Dual-targeted therapy (DTT), combining two biologic agents or biologics with small molecules, has emerged as a novel approach to address this unmet need by targeting multiple inflammatory pathways simultaneously. Evidence suggests that DTT holds promise in improving clinical and endoscopic outcomes, especially in patients with refractory disease or extraintestinal manifestations. Safety data, while consistent with monotherapy profiles, highlight the importance of vigilant monitoring for infections and other adverse events. Continued research and high-quality trials are crucial to defining optimal DTT regimens and broadening its clinical applicability. This review explores the efficacy and safety of DTT in IBD, reporting data from clinical trials, systematic reviews, and real-world studies. Full article
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