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Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd 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: 31 January 2025 | Viewed by 9220

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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, Beibei, 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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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) as 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 aims to 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 prevention, diagnosis, and treatment of IBD.

Dr. Dingpei Long
Guest Editor

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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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Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches in Biomedicines (11 articles)

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Research

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20 pages, 4325 KiB

Open AccessArticle

Identifying Common Genetic Etiologies Between Inflammatory Bowel Disease and Related Immune-Mediated Diseases

by Xianqiang Liu, Dingchang Li, Yue Zhang, Hao Liu, Peng Chen, Yingjie Zhao, Piero Ruscitti, Wen Zhao and Guanglong Dong

Biomedicines 2024, 12(11), 2562; https://doi.org/10.3390/biomedicines12112562 - 8 Nov 2024

Viewed by 475

Abstract

Background: Patients with inflammatory bowel disease (IBD) have an increased risk of developing immune-mediated diseases. However, the genetic basis of IBD is complex, and an integrated approach should be used to elucidate the complex genetic relationship between IBD and immune-mediated diseases. Methods: The genetic relationship between IBD and 16 immune-mediated diseases was examined using linkage disequilibrium score regression. GWAS data were synthesized from two IBD databases using the METAL, and multi-trait analysis of genome-wide association studies was performed to enhance statistical robustness and identify novel genetic associations. Independent risk loci were meticulously examined using conditional and joint genome-wide multi-trait analysis, multi-marker analysis of genomic annotation, and functional mapping and annotation of significant genetic loci, integrating the information of quantitative trait loci and different methodologies to identify risk-related genes and proteins. Results: The results revealed four immune-mediated diseases (AS, psoriasis, iridocyclitis, and PsA) with a significant relationship with IBD. The multi-trait analysis revealed 909 gene loci of statistical significance. Of these loci, 28 genetic variants were closely related to IBD, and 7 single-nucleotide polymorphisms represented novel independent risk loci. In addition, 14 genes and 514 proteins were found to be associated with susceptibility to immune-mediated diseases. Notably, IL1RL1 emerged as a key player, present within pleiotropic genes across multiple protein databases, highlighting its potential as a therapeutic target. Conclusions: This study suggests that the common polygenic determinants between IBD and immune-mediated diseases are widely distributed across the genome. The findings not only support a shared genetic relationship between IBD and immune-mediated diseases but also provide novel therapeutic targets for these diseases. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd Edition))

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10 pages, 4774 KiB

Open AccessArticle

The Effect of Drugs on the Intestinal Microbiota in Crohn’s Disease

by Xue Yang, Yinghui Zhang, Caiping Gao, Yan Pan, Shan Du, Shiyu Xiao and Zhou Zhou

Biomedicines 2024, 12(10), 2241; https://doi.org/10.3390/biomedicines12102241 - 1 Oct 2024

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Abstract

Objective: We took advantage of a single-center cross-sectional study to investigate the effect of different drugs on intestinal microbiota and function in Crohn’s disease. Methods: We studied the difference in fecal microbiota of Crohn’s disease patients treated with mesalazine, azathioprine, and infliximab, as well as untreated patients, by metagenome and screened for differential microbiota. Further, we investigated functional differences in intestinal microbiota among the four groups. Results: Through metagenomic sequencing, we found that there was no difference between the four groups in ACE and Chao1 indices, but IFX and mesalazine improved species diversity and homogeneity compared to the untreated group, as evidenced by statistically significant differences in the Shannon index, Simpson index, and pielou_evenness. In addition, beta diversity suggested a difference between groups, but the difference was not significant. Non-parametric tests revealed differences between the four groups at the phylum level, class level, and genus level. Further analysis by LEfSe analysis revealed that the level of short-chain fatty acid-producing microbiota was increased in the treated groups, while there was no difference between the treated groups when compared to each other. Finally, the KEGG database and EggNOG database revealed that there were functional differences in intestinal microbiota among the four groups, including microbial metabolism pathway, cysteine and methionine metabolism pathway, cytoskeleton, etc. Conclusions: Mesalazine, azathioprine, and infliximab can all affect the intestinal microbiota and function in patients with Crohn’s disease, and the drugs may alleviate intestinal inflammation in patients with Crohn’s disease by modulating the intestinal microbiota. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd Edition))

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14 pages, 6208 KiB

Open AccessArticle

Characteristics of Mucosa-Associated Microbiota in Ulcerative Colitis Patients with 5-Aminosalicylic Acid Intolerance

by Hiroshi Matsumoto, Momoyo Sasahira, Tei Tei Go, Shogen Yo, Takehiro Ninomiya, Motoyasu Osawa, Osamu Handa, Eiji Umegami, Ryo Inoue and Akiko Shiotani

Biomedicines 2024, 12(9), 2125; https://doi.org/10.3390/biomedicines12092125 - 19 Sep 2024

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Abstract

Background/Objectives: 5-Aminosalicylic acid (5-ASA) is a first-line therapy for ulcerative colitis (UC). This study examined the mucosa-associated microbiota (MAM) in UC patients, distinguishing between those who were 5-ASA tolerant and intolerant. Methods: Brushing samples were collected from the sigmoid and ileal end of patients with UC during endoscopic procedures. The samples were profiled by using the Illumina MiSeq platform. The V3–V4 regions of the 16S rRNA gene (460 bp) were amplified by using tailed PCR. Results: A total of 15 patients with 5-ASA intolerance, 38 patients with 5-ASA tolerance, and 19 healthy controls were recruited in this study. The α-diversity indices were remarkably different among the three groups in the ileum mucosa but not in the sigmoid colon. In the ileum mucosa, Alistipes, Ruminococcaceae, and Odoribacter were less abundant in the 5-ASA-intolerant group than in the control and 5-ASA-tolerant groups. On the contrary, Merdibacter, Brevundimonas, and Porphyromonas were more abundant in the 5-ASA-intolerant group than in other groups. Conclusions: The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd Edition))

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18 pages, 3631 KiB

Open AccessArticle

Infliximab in Inflammatory Bowel Disease: Leveraging Physiologically Based Pharmacokinetic Modeling in the Clinical Context

by Zvonimir Petric, João Gonçalves and Paulo Paixão

Biomedicines 2024, 12(9), 1974; https://doi.org/10.3390/biomedicines12091974 - 1 Sep 2024

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Abstract

In this study, a physiologically based pharmacokinetic (PBPK) modeling framework was employed to explore infliximab exposure following intravenous (5 mg/kg) and subcutaneous administration (encompassing the approved 120 mg flat-fixed dose as a switching option) in virtual adult and pediatric patients with inflammatory bowel disease (IBD). The PBPK model and corresponding simulations were conducted using the PK-Sim^® software platform. The PBPK simulation indicated that a 120 mg subcutaneous flat-fixed dose might not be optimal for heavier adults with IBD, suggesting the need for infliximab dose escalation. For an older virtual pediatric patient (14 years old), subcutaneous administration of a 120 mg flat-fixed dose appears to be a feasible IBD treatment option. In the final exploration scenario, the model was extended to predict hypothetical subcutaneous infliximab doses in a virtual pediatric population (6–18 years old), stratified into three weight bands (20–30 kg, 30–45 kg, and 45–70 kg), that would yield post-switch trough concentrations of infliximab comparable to those seen in adults with the 120 mg flat-fixed subcutaneous dose. The PBPK-model-informed dose suggestions were 40 mg for the 20–30 kg band, 80 mg for the 30–45 kg band, and 120 mg for the 45–70 kg band. As demonstrated in this paper, the PBPK modeling framework can serve as a versatile tool in clinical pharmacology to investigate various clinical scenarios, such as exploring alternative dosing regimens and routes of administration, ultimately advancing IBD treatment across diverse (sub)populations of clinical interest. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd Edition))

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12 pages, 971 KiB

Open AccessArticle

Impact of Coffee Consumption on Subjective Perception and Inflammatory Markers in Patients with Inflammatory Bowel Diseases

by Lidia Neamți, Simona R. Gheorghe, Amalia Ventuneac, Tudor Drugan, Cristina Drugan, Ciprian N. Silaghi, Lidia Ciobanu and Alexandra M. Crăciun

Biomedicines 2024, 12(8), 1733; https://doi.org/10.3390/biomedicines12081733 - 2 Aug 2024

Viewed by 1152

Abstract

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic conditions marked by persistent inflammation, impacting patients’ quality of life. This study assessed differences in coffee consumption between CD and UC patients and its potential effects on the subjective perception and objective changes in inflammation markers in these two categories of patients. Using questionnaires, coffee consumption patterns, and perceived symptom effects were evaluated. Biological samples were collected to measure the following inflammatory markers: leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and fecal calprotectin (FC). Among 148 patients, 60% reported regular coffee consumption, with no significant difference between CD and UC patients. While 45.93% perceived no impact on symptoms, 48% of those reporting exacerbation continued their regular coffee consumption. FC values were significantly lower in coffee consumers than in non-consumers (p < 0.05), particularly in those consuming natural coffee (p < 0.001), and the case was observed for UC patients (p < 0.05). No significant differences were observed in other inflammatory markers, regardless of coffee type, frequency, or milk addition. This study highlights the commonality of coffee consumption among IBD patients and the association of lower FC levels with coffee consumption, especially in UC patients, suggesting that coffee may influence intestinal inflammatory responses. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd Edition))

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21 pages, 5581 KiB

Open AccessArticle

Ruscogenin Attenuates Ulcerative Colitis in Mice by Inhibiting Caspase-1-Dependent Pyroptosis via the TLR4/NF-κB Signaling Pathway

by Jingwei Li, Huihuan Wu, Jialiang Zhou, Rui Jiang, Zewei Zhuo, Qi Yang, Hao Chen and Weihong Sha

Biomedicines 2024, 12(5), 989; https://doi.org/10.3390/biomedicines12050989 - 30 Apr 2024

Viewed by 1297

Abstract

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders affecting the digestive tract, including ulcerative colitis and Crohn’s disease. Ruscogenin, a prominent steroidal sapogenin present in radix ophiopogon japonicus, has shown a protective effect on attenuating the inflammatory response associated with inflammatory diseases, but the efficacy of ruscogenin in IBD remains unclear. The aim of this study is to explore the effect of ruscogenin on intestinal barrier dysfunction and inflammatory responses as well as the underlying mechanism in ulcerative colitis. A dextran sulfate sodium salt (DSS)-induced C57BL/6 mouse colitis model was employed for the in vivo studies, while in vitro experiments were performed in THP-1 cells and human intestinal epithelial cells involved in inducing inflammatory responses and pyroptosis using LPS/nigericin. The results indicated that ruscogenin treatment attenuated the symptoms of ulcerative colitis, reduced the release of inflammatory cytokines and the expression of pyroptosis-associated proteins, and restored the integrity of the intestinal epithelial barrier in colon tissue in mice. Moreover, ruscogenin inhibited LPS/nigericin-induced pyroptosis in THP-1 cells. Mechanically, ruscogenin inhibited NLRP3 inflammasome activation and canonical pyroptosis, at least in part, through the suppression of the TLR4/NF-κB signaling pathway. These findings might provide new insights and a solid foundation for further exploration into the therapeutic potential of ruscogenin in the treatment of IBD. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd Edition))

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Review

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20 pages, 790 KiB

Open AccessReview

Managing Crohn’s Disease Postoperative Recurrence Beyond Prophylaxis: A Comprehensive Review with Meta-Analysis

by Andrei Ovidiu Olteanu, Artsiom Klimko, Eugen Nicolae Tieranu, Andreea Daniela Bota, Carmen Monica Preda, Ioana Tieranu, Christopher Pavel, Mihai Radu Pahomeanu, Cristian Valentin Toma, Adrian Saftoiu, Elena Mirela Ionescu and Cristian George Tieranu

Biomedicines 2024, 12(11), 2434; https://doi.org/10.3390/biomedicines12112434 - 23 Oct 2024

Viewed by 606

Abstract

Background and Aims: Postoperative recurrence in Crohn’s disease remains a significant clinical challenge, with high recurrence rates despite advancements in medical therapy. This study aims to evaluate the efficacy of various treatments for managing postoperative recurrence following ileocolonic resection in Crohn’s disease. Methods: A comprehensive search of PubMed, Cochrane, and Scopus databases was performed to identify studies reporting on the therapeutic management of postoperative recurrence in Crohn’s disease. Studies encompassing patients with an endoscopic Rutgeerts score of at least I2 were included. Results: Ustekinumab showed promise, achieving significant endoscopic and clinical success in difficult-to-treat patients. Anti-TNF agents demonstrated superior endoscopic and clinical remission rates compared to mesalamine and azathioprine. Retreatment with anti-TNF therapy remained effective even after preoperative failure. Thalidomide showed efficacy in refractory Crohn’s disease, but carries significant toxicity risks, necessitating careful patient selection and monitoring. Combination therapies and non-pharmacologic strategies like enteral nutrition offer additional options, though patient compliance remains challenging. Conclusions: Personalized treatment plans based on individual risk factors and biomarkers are crucial. Infliximab is recommended as the first-line treatment, with ustekinumab and vedolizumab as alternatives in case of anti-TNF failure or intolerance. Early intervention, patient education, and ongoing evaluation are essential for optimizing long-term outcomes in managing postoperative recurrence in Crohn’s disease. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd Edition))

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19 pages, 1048 KiB

Open AccessReview

Extraintestinal Manifestations in Inflammatory Bowel Disease: From Pathophysiology to Treatment

by Ilaria Faggiani, Jacopo Fanizza, Ferdinando D’Amico, Mariangela Allocca, Alessandra Zilli, Tommaso Lorenzo Parigi, Alberto Barchi, Silvio Danese and Federica Furfaro

Biomedicines 2024, 12(8), 1839; https://doi.org/10.3390/biomedicines12081839 - 13 Aug 2024

Viewed by 1805

Abstract

The inflammatory bowel diseases (IBDs) are systemic conditions that affect not only the gastrointestinal tract but also other parts of the body. The presence of extraintestinal manifestations can significantly impact the quality of life in IBD patients. Peripheral arthritis, episcleritis, and erythema nodosum are frequently associated with active intestinal inflammation and often improve with standard treatment targeting intestinal inflammation. In contrast, anterior uveitis, ankylosing spondylitis, and primary sclerosing cholangitis typically occur independently of disease flares. The incidence of these conditions in individuals with IBD can reach up to 50% of patients over the course of their lifetime. In addition, some advanced therapies utilized for the treatment of IBD potentially result in side effects that may resemble extraintestinal manifestations. This review provides a thorough analysis of the pathophysiology and treatment of extraintestinal manifestations associated with Crohn’s disease and ulcerative colitis. Full article

(This article belongs to the Special Issue Crohn's Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (2nd Edition))

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