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Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Gastroenterology & Hepatopancreatobiliary Medicine".

Deadline for manuscript submissions: 12 June 2025 | Viewed by 16761

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Dr. Moisés Tolentino B. Da Silva

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Laboratory of Physiology, Department of Immuno-Physiology e Pharmacology, Institute of the Biomedical Science Abel Salazar, (ICBAS), School of Medicine and Biomedical Sciences, Center for Drug Discovery and Innovative Medicines (MedInUP), University of Porto, Porto, Portugal
Interests: gatrointestinal motility; intestinal bowel disease; physical exercise; intestinal inflammation; enteric nervous system
Special Issues, Collections and Topics in MDPI journals

Dr. Isabel Silva

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Laboratory of Pharmacology and Neurobiology, Department of Immuno-Physiology e Pharmacology, Institute of the Biomedical Science Abel Salazar, (ICBAS), School of Medicine and Biomedical Sciences, Center for Drug Discovery and Innovative Medicines (MedInUP), University of Porto, Porto, Portugal
Interests: inflammatory bowel disease; purinergic system; ENS; clinical research

Special Issue Information

Dear Colleagues,

Inflammatory bowel diseases (IBD) are characterized by chronic inflammation of the gastrointestinal tract, with two main clinical manifestations: Crohn's disease, whose pathogenesis involves any part of the gastrointestinal tract, and ulcerative colitis, in which inflammation is limited to the colon. This gastrointestinal tract inflammation leads to symptoms such as bleeding, abdominal pain, diarrhea, malnutrition, and increased intestinal permeability. Among the factors involved in the pathogenesis of these diseases, genetics, dysregulation in the intestinal microbiota and environmental factors such as diet and physical inactivity stand out. Considering the severity of symptoms related to IBD, alternative therapies have been sought to alleviate intestinal discomfort, and physical exercise, dietary interventions, and nutritional supplements can bring benefits, which include improving the composition of the microbiota, intestinal tract, and its antioxidant and anti-inflammatory action, which may have a protective action on the permeability in the gastrointestinal tract. This Research Topic aims to bring a collection of papers that approach the clinical diagnosis and treatment of IBD. We welcome the submission of manuscripts including, but not limited to, the following topics: Special focus will be given (but is not restricted) to clinical diagnosis of IBD; exercise or nutrition on IBD; microbiota and IBD; body composition on IBD.

Dr. Moisés Tolentino B. Da Silva
Dr. Isabel Silva
Guest Editors

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Keywords

gastrointestinal disorders
intestinal inflammation
intestinal bowel disease
nutrition
physical exercise
cancer
enteric nervous system
vagus nerve

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Published Papers (10 papers)

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Research

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13 pages, 785 KiB

Open AccessArticle

Neutrophil Elastase and Elafin in Inflammatory Bowel Diseases: Urinary Biomarkers Reflecting Intestinal Barrier Dysfunction and Proteolytic Activity

by Aleksandra Górecka and Katarzyna Komosinska-Vassev

J. Clin. Med. 2025, 14(7), 2466; https://doi.org/10.3390/jcm14072466 - 4 Apr 2025

Viewed by 392

Abstract

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory disorder driven by a complex interplay of immune and proteolytic mechanisms. Neutrophil elastase (NE), released at sites of inflammation, plays a central role by promoting inflammation, degrading the extracellular matrix (ECM), and disturbing intestinal barrier integrity via NF-κB activation and E-cadherin degradation. Elafin, an endogenous NE inhibitor, mitigates proteolytic damage, reinforces the intestinal barrier, and exerts anti-inflammatory effects by suppressing NF-κB and reducing pro-inflammatory cytokines. Since the NE/elafin balance is critical in IBD, assessing their ratio may provide a more precise measure of proteolytic dysregulation. This study aimed to evaluate the diagnostic and prognostic utility of urinary NE, elafin, and their ratio in IBD patients. Methods: Urinary concentrations of NE and elafin were measured by immunoassay in 88 subjects including ulcerative colitis and Crohn’s disease patients and healthy individuals. The diagnostic accuracy of these biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Results: Urinary NE levels were significantly elevated in both UC and CD patients compared to controls, with a 17-fold increase in the UC patients and a 28-fold increase in the CD patients (p < 0.0001). Elafin levels were also increased in IBD patients. The NE/elafin ratio was significantly increased in both disease groups, with a 4.5-fold increase in the UC and 5.6-fold increase in the CD patients compared to healthy controls. The ROC curve analysis demonstrated that the NE/elafin ratio is the most effective biomarker for distinguishing CD patients from healthy individuals (AUC = 0.896), with a high sensitivity (92.9%) and specificity (69.7%), making it a strong diagnostic tool. NE also showed an excellent diagnostic performance both in CD (AUC = 0.842) and UC (AUC = 0.880). The elafin urinary profile had a high diagnostic value, with a better accuracy in the UC patients (AUC = 0.772) than the CD patients (AUC = 0.674), though it was inferior to NE and NE/elafin. Conclusions: Our findings indicate that urinary NE, elafin, the and NE/elafin ratio have significant diagnostic value in differentiating IBD patients from healthy controls. The NE/elafin ratio and NE proved to be the most reliable urinary biomarkers in both CD and UC diagnosis, with a high predictive value and strong discriminatory power. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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14 pages, 1191 KiB

Open AccessArticle

Exploring Dietary- and Disease-Related Influences on Flatulence and Fecal Odor Perception in Inflammatory Bowel Disease

by Lea Pueschel, Sonja Nothacker, Leonie Kuhn, Heiner Wedemeyer, Henrike Lenzen and Miriam Wiestler

J. Clin. Med. 2025, 14(1), 137; https://doi.org/10.3390/jcm14010137 - 29 Dec 2024

Cited by 1 | Viewed by 1939

Abstract

Background/Objectives: Inflammatory bowel disease (IBD) affects gastrointestinal function and may alter fecal and flatulence odor (intestinal odor) due to changes in inflammation, the gut microbiome, and metabolism. Investigating the relationship between dietary habits and intestinal odor in IBD is critical given the relationship between diet, gut health, and microbiome diversity. Methods: We performed a cohort analysis of a monocentric, cross-sectional study at a tertiary referral center and compared the perception of fecal and flatulence odor in 233 IBD patients (n = 117 women) with that of 96 healthy controls (HCs) (n = 67 women). In addition to a short screening questionnaire on highly processed foods (sQ-HPF), dietary behavior (Food Frequency Questionnaire (FFQ)), clinical (HBI, PMS) and biochemical (CRP, fecal calprotectin) parameters of disease activity, and adherence to a Mediterranean diet were assessed. Results: A notable predisposition towards elevated levels of intestinal malodor was identified in the IBD cohort when compared to the HC group. The analysis of dietary behavior in conjunction with intestinal malodor revealed more pronounced associations in the HC collective than in the IBD collective. The data further indicated that, in comparison to those in remission, IBD individuals with an active disease status exhibited a higher prevalence of intestinal malodor. In an adjusted logistic regression analysis of the influence of disease- and diet-specific factors on flatulence and fecal malodor in IBD, male sex was identified as a significant risk factor. Conclusions: This study highlights the significance of dietary factors in the management of IBD symptoms, with a particular focus on flatulence and fecal odor. Individuals with IBD demonstrated a higher propensity for intestinal malodor compared to HC, with active disease status further amplifying this prevalence. Dietary behavior showed stronger associations with malodor in the HC group than in IBD individuals, suggesting distinct interaction patterns between diet and gut health in these populations. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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16 pages, 1554 KiB

Open AccessArticle

Pregnancy in Inflammatory Bowel Disease: Data from a Real-World Cohort in Germany

by Mousa Ayoub, Anna Muzalyova, Alanna Ebigbo, Sandra Nagl, Christoph Römmele, Johanna Classen, Julia Wanzl, Carola Fleischmann, Sami Ayoub, Vidan Tadic, Jakob Schlottmann and Elisabeth Schnoy

J. Clin. Med. 2024, 13(24), 7710; https://doi.org/10.3390/jcm13247710 - 17 Dec 2024

Viewed by 963

Abstract

Background: Inflammatory bowel disease (IBD) frequently manifests at a young age, during the peak fertility years. Understanding the risks of negative pregnancy outcomes associated with IBD is crucial for effective pregnancy management and support. Additionally, it is essential to provide patients with the necessary knowledge to make informed choices and foster their confidence in navigating pregnancy while maintaining effective disease management. Although IBD frequently appears during the peak fertility years, knowledge about managing pregnancy in the context of IBD remains limited and often inaccurate among both physicians and patients. Our study aims to assess the complications occurring during pregnancy in patients with IBD, considering the level of disease activity, and to evaluate the standard of care provided to patients with chronic inflammatory conditions through a cohort analysis. Methods: Patients with IBD who had children were included in this single-center mixed-method (retrospective and prospective) study. Clinical data, disease progression, course of pregnancy, and complications were examined in women. Outcomes for children of men with IBD were also analyzed. To supplement the data, a survey addressing various pregnancy-related topics, including all patients from the university outpatient clinic for IBD, was conducted over a period of six months. Results: A total of 410 patients were screened retrospectively between 2010 and 2021. In total, 134 patients who had children were included in the study: 51.4% (n = 69) had Crohn’s disease, 44% (n = 59) had ulcerative colitis, and 4.6% (n = 6) had unclassified inflammatory bowel disease. Of the women, 85% (n = 34) were in remission for at least three months before pregnancy, 14.6% (n = 6) experienced an acute flare-up during pregnancy, and 10.3% (n = 4) and 7.7% (n = 3) had active disease at the time of delivery and during breastfeeding, respectively. Patients with IBD who were in remission before pregnancy did not experience a higher risk of pregnancy complications (no cases of pre-eclampsia or placental abruption were reported in this group). However, the rates of gestational diabetes and fever during pregnancy were 10% for those in remission, compared to 25% for those with active disease. Conclusions: Patients with IBD in remission did not present an increased risk of pregnancy complications. However, our survey indicates that those with active disease at conception were more likely to experience complications such as gestational diabetes and fever. These findings underscore the importance of adequate patient education regarding the safety of various IBD medications during pregnancy in order to avoid pregnancy-related complications. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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10 pages, 768 KiB

Open AccessArticle

Evaluation of Acute Terminal Ileitis in Hospitalized Patients: Development of a Predictive Model to Distinguish Crohn’s Disease from Other Etiologies

by Anton Bermont, Naim Abu-Freha, Refael Aminov, Sergei Vosko, Haim Shirin and Daniel L. Cohen

J. Clin. Med. 2024, 13(17), 5030; https://doi.org/10.3390/jcm13175030 - 25 Aug 2024

Viewed by 1410

Abstract

Background/Objectives: Terminal ileitis (TI) is often identified on CT scans in emergency settings. Diagnosing Crohn’s disease (CD) as a cause of TI is crucial due to its significant long-term implications. This study aimed to differentiate CD from other causes of acute TI and develop a predictive model for CD diagnosis. Methods: A retrospective case-control study was conducted at Shamir Medical Center including adults diagnosed with acute TI from January 2012 to December 2020. Patients with a history of inflammatory bowel disease or prior intestinal surgery were excluded. Patients were categorized into CD and non-CD groups based on their subsequent clinical course. A logistic regression model was developed and subsequently validated with additional patients hospitalized between 2021 and 2023. Results: Among 135 patients, 37 (27.4%) were diagnosed with CD. CD patients were younger (median age 27 vs. 39 years, p = 0.003), predominantly male (83.8% vs. 51%, p = 0.001), and had higher rates of chronic abdominal pain, diarrhea, anemia, and weight loss prior to hospitalization. Significant laboratory differences included higher platelet counts (p = 0.006) and lower mean corpuscular volume (MCV) (p = 0.001) in CD patients. Radiologic signs of complicated disease were more common in CD (35.1% vs. 4.1%, p < 0.001). The predictive model incorporating gender, abdominal pain history, and MCV showed an area under the curve (AUC) of 0.87, with a sensitivity of 100% and specificity of 63.6% in the validation group of 18 patients. Conclusions: This study identified key predictors of CD in patients presenting with acute TI and developed a predictive model with a substantial diagnostic capability. Use of this model for early identification and treatment of CD may potentially improve patient outcomes. Further prospective validation of this model is warranted. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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14 pages, 13276 KiB

Open AccessArticle

Specific Oral Manifestations in Adults with Crohn’s Disease

by Yavuz Cagir, Muhammed Bahaddin Durak, Cem Simsek and Ilhami Yuksel

J. Clin. Med. 2024, 13(13), 3955; https://doi.org/10.3390/jcm13133955 - 5 Jul 2024

Cited by 2 | Viewed by 2611

Abstract

Background: Oral manifestations of Crohn’s disease (CD) include non-specific lesions and specific lesions directly related to intestinal inflammation. Oral lesions that can be overlooked in CD are sometimes challenging to treat. Methods: In this retrospective single-center study, patients with CD aged over 18 years who complied with follow-up and treatment were included. Clinical definitions of specific oral lesions included pyostomatitis vegetans, glossitis with fissuring, lip swelling with fissuring, cobblestoning, and orofacial granulomatosis. Experienced dentists confirmed the specific lesions in each case. Three groups of patients were identified: those without oral lesions, those with non-specific oral lesions, and those with specific oral lesions. The groups were compared based on demographics, disease extent and behavior (based on the Montreal classification), extraintestinal involvement, biologic and steroid treatment, and the requirement of resective surgery. Results: A total of 96 patients (14.2%) with oral lesions were found among the 676 patients with CD (59.7% male, median age 38 years) who were followed for 6.83 years (IQR 0.5–29.87 years). Eight patients (1.2%, 9 lesions) had specific oral lesions, while eighty-eight patients (13%) had non-specific lesions. Orofacial granulomatosis (n = 3), cobblestoning (n = 2), glossitis with fissuring (n = 2), and lip swelling with fissuring (n = 2) were among the specific lesions. The majority of patients (75%) with specific lesions were male, and their median age was 46.5 years (range: 23–68 years). Disease localization was commonly ileocolonic (50%), and perianal disease was present in 25% of patients. Three patients were active smokers. Extraintestinal manifestations were peripheral arthritis/arthralgia (n = 7) and sacroiliitis (n = 1). All specific lesions were associated with moderate-to-severe disease. Five patients improved with biologic therapy, and two patients with immunomodulatory therapy. Conclusions: Specific oral lesions in CD were associated with active disease and improved with immunomodulators or biologic therapy. Close cooperation between gastroenterologists and dentists is essential for early diagnosis and optimal management of CD. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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Review

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20 pages, 695 KiB

Open AccessReview

Physical Exercise as a Therapeutic Approach in Gastrointestinal Diseases

by Juliana Soares Severo, Alda Cássia Alves da Silva, Brenda Lois Barros dos Santos, Thiago Sousa Reinaldo, Aureliano Machado de Oliveira, Rodrigo Soares Pereira Lima, Francisco Leonardo Torres-Leal, Armênio Aguiar dos Santos and Moisés Tolentino Bento da Silva

J. Clin. Med. 2025, 14(5), 1708; https://doi.org/10.3390/jcm14051708 - 3 Mar 2025

Viewed by 1650

Abstract

Background/Objectives: Physical exercise can have significant consequences for the gastrointestinal tract, which is why there have been studies into its influence on the treatment of conditions such as colorectal cancer, inflammatory bowel diseases (IBD), and irritable bowel syndrome (IBS), being that there is epidemiological evidence that exercise has a protective effect against colon cancer. This review aims to demonstrate the mechanisms of action of physical exercise in the gastrointestinal tract, as well as the benefits of exercise in diseases associated with the digestive system, in addition to gathering training recommendations in treating different gastrointestinal diseases. Results: Physical exercise modulates gastrointestinal motility, permeability, immune responses, and microbiota composition, with both beneficial and adverse effects depending on intensity and duration. Regular moderate exercise is associated with improved quality of life in IBD and IBS, reduced colorectal cancer risk, and potential symptom relief in constipation. However, high-intensity exercise may exacerbate gastroesophageal reflux symptoms and increase the risk of gastrointestinal bleeding. While aerobic exercise has been extensively studied, the effects of resistance training on gastrointestinal health remain underexplored. Conclusions: New methodologies and techniques, such as molecular biology and the study of gastric receptors, have led to advances in understanding the gastrointestinal changes associated with physical exercise. These advances cover different exercise intensities and are being investigated in both experimental models and clinical studies. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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14 pages, 2982 KiB

Open AccessReview

Role of Mirikizumab in the Treatment of Inflammatory Bowel Disease—From Bench to Bedside

by Michael Colwill, Samantha Baillie, Jennifer Clough, Richard Pollok, Andrew Poullis, Kamal Patel and Sailish Honap

J. Clin. Med. 2025, 14(3), 1001; https://doi.org/10.3390/jcm14031001 - 5 Feb 2025

Cited by 1 | Viewed by 2434

Abstract

Mirikizumab is a monoclonal antibody directed against the p19 subunit of interleukin (IL)-23 to inhibit its interaction with the IL-23 receptor. IL-23 is a key cytokine involved in initiating and perpetuating the inflammatory cascade in inflammatory bowel disease (IBD). Mirikizumab is the first agent from the novel anti-IL-23p19 drug class to be licensed for ulcerative colitis and the first to present long-term endoscopic, histologic, symptomatic, and quality-of-life outcomes. More recently, the VIVID trial programme has led to the approval of mirikizumab in moderate to severe Crohn’s disease. This review explores the history of its development, discusses key immunopharmacological properties unique to the drug, and details the available clinical trials and real-world evidence supporting its use in IBD. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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18 pages, 284 KiB

Open AccessReview

Optimal Management of Patients with Moderate-to-Severe Inflammatory Bowel Disease

by Tugrul Purnak and Atilla Ertan

J. Clin. Med. 2024, 13(23), 7026; https://doi.org/10.3390/jcm13237026 - 21 Nov 2024

Viewed by 1563

Abstract

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic and often debilitating condition requiring complex and individualized management. Over the past few decades, advancements in understanding IBD pathophysiology have led to a transformative shift in therapeutic approaches. This article provides a comprehensive overview of the evolution of IBD treatments, from early symptom-focused therapies to modern biologics, small molecule agents, and emerging treatment strategies. We discuss therapeutic goals centered on achieving clinical remission, endoscopic/mucosal healing, and enhancing patient quality of life. Additionally, we explore the rationale for the early and personalized use of biologic therapies in moderate-to-severe cases, review the current FDA-approved agents as of 2024, and highlight the advantages and limitations of these treatments. Special attention is given to the evolving role of novel oral therapies, including Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators, and future new directions. This paper aims to guide clinicians in navigating the expanding therapeutic landscape of IBD, emphasizing patient-centered decision-making and addressing ongoing challenges in achieving optimal disease control. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

43 pages, 653 KiB

Open AccessReview

Common Mistakes in Managing Patients with Inflammatory Bowel Disease

by Javier P. Gisbert and María Chaparro

J. Clin. Med. 2024, 13(16), 4795; https://doi.org/10.3390/jcm13164795 - 14 Aug 2024

Viewed by 2123

Abstract

Introduction: Errors are very common in medical practice and in particular, in the healthcare of patients with inflammatory bowel disease (IBD); however, most of these can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to this problem consists in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation for each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, elderly patients, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for a greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it is desirable to follow IBD patients in specialized units, which would undoubtedly be associated with higher-quality healthcare and a lower likelihood of errors in managing these patients. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

Other

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22 pages, 2979 KiB

Open AccessStudy Protocol

Effectiveness of Telemedicine in Inflammatory Bowel Disease in Russia: TIGE-Rus (Telemonitoring for IBD Goodness Examination in Russia) Study Protocol of a Randomized Controlled Trial

by Dina A. Akhmedzyanova, Yuliya F. Shumskaya, Yuriy A. Vasilev, Anton V. Vladzymyrskyy, Olga V. Omelyanskaya, Yulya A. Alymova, Marina G. Mnatsakanyan, Alexandr S. Panferov, Olga V. Taschyan, Irina V. Kuprina, Marta V. Yurazh, Artur S. Eloev and Roman V. Reshetnikov

J. Clin. Med. 2024, 13(24), 7734; https://doi.org/10.3390/jcm13247734 - 18 Dec 2024

Viewed by 759

Abstract

Background: Inflammatory bowel diseases (IBD), associated with a significant burden on patients’ lives, are becoming increasingly common. Patients with IBD need continuous treatment and lifelong monitoring, which could be achieved by telemonitoring. Telemonitoring has been shown to be effective in improving outcomes for patients with IBD, and can provide a more convenient and accessible way for patients to receive care. However, the certainty of evidence remains low. This article outlines the methodology of a randomized control study that aims to assess the efficacy of telemonitoring compared to face-to-face follow-up for patients with IBD in Russia, hypothesizing that the implementation of telemonitoring will lead to improvement in clinical, social, and organizational areas. Methods: The TIGE-Rus study is a randomized controlled trial. The study consists of three stages, including selection of patients and random assignment into two groups with a ratio of 1:1, follow-up care using telemonitoring or face-to-face appointments, and evaluation and comparison of follow-up efficacy in both groups. In the first stage, all patients will undergo laboratory tests and instrumental examinations, and fill out questionnaires to measure disease activity, quality of life, medication adherence, psychological well-being, and satisfaction with medical care. In the second stage, the control group will receive standard care while the telemonitoring group will have access to a web platform where they can report their clinical activity, fill out questionnaires, and have online consultations with gastroenterologists. The gastroenterologists will also make monthly phone calls to each patient in the telemonitoring group to monitor their progress. In the third stage of the study, both the telemonitoring group and the control group will be re-hospitalized after six months of monitoring. IBD activity will be evaluated through laboratory and instrumental examinations. Additionally, all the participants will complete questionnaires to assess the disease activity, medication adherence, quality of life, psychological well-being, and satisfaction with medical care in both groups. Conclusions: The trial will explore whether telemonitoring is effective in improving clinical, social, and organizational aspects in the management of patients with IBD in the setting of the Russian healthcare system. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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