Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Diagnostics diagnostics	3.8	6.9	2011	20.4 Days	CHF 2600	Submit
Gastrointestinal Disorders gastrointestdisord	1.9	2.1	2019	19.6 Days	CHF 1400	Submit
International Journal of Molecular Sciences ijms	5.6	10.0	2000	17.5 Days	CHF 2900	Submit
Journal of Clinical Medicine jcm	3.3	5.2	2012	16.6 Days	CHF 2600	Submit
Medicina medicina	2.9	4.6	1920	17.4 Days	CHF 2200	Submit
Nutrients nutrients	5.8	10.2	2009	15.8 Days	CHF 2900	Submit
Pharmaceuticals pharmaceuticals	5.7	9.0	2004	14.3 Days	CHF 2900	Submit

21 pages, 942 KB

Open AccessReview

Raising the Bar in Crohn’s Disease: Is Transmural Healing Achievable?

by Fabrizio Fanizzi, Alessandra Zilli, Tommaso Lorenzo Parigi, Virginia Solitano, Sara Massironi, Federica Furfaro, Laurent Peyrin-Biroulet, Mariangela Allocca, Silvio Danese and Ferdinando D’Amico

Diagnostics 2026, 16(17), 2749; https://doi.org/10.3390/diagnostics16172749 - 27 Aug 2026

Abstract

Background: The therapeutic paradigm of Crohn’s disease (CD) has progressively evolved from symptom control toward objective treatment targets aimed at modifying disease course. Although endoscopic mucosal healing (MH) is currently regarded as a major treatment goal, it may inadequately reflect residual inflammation in [...] Read more.

Background: The therapeutic paradigm of Crohn’s disease (CD) has progressively evolved from symptom control toward objective treatment targets aimed at modifying disease course. Although endoscopic mucosal healing (MH) is currently regarded as a major treatment goal, it may inadequately reflect residual inflammation in a condition characterized by transmural bowel involvement. Consequently, transmural healing (TH), assessed through cross-sectional imaging modalities, has emerged as a potential marker of deeper disease control. Methods: A comprehensive literature review was conducted to identify studies evaluating the definition, assessment, prognostic significance, and achievability of TH in CD. Original studies, randomized controlled trials, systematic reviews, consensus statements, and international guidelines were included. Results: Accumulating evidence indicates that TH is associated with superior long-term outcomes compared with MH alone, including lower risks of hospitalization, surgery, treatment escalation, disease relapse, and bowel damage progression. However, substantial heterogeneity persists regarding the definition of TH across imaging modalities, with intestinal ultrasound and magnetic resonance enterography representing the principal tools for its assessment. Available data suggest that TH can be achieved in a meaningful proportion of patients receiving advanced therapies, particularly when treatment is initiated early in the disease course, although rates vary considerably according to therapeutic class, disease characteristics, and the definition adopted. Emerging technologies may further refine the assessment of transmural disease activity. Conclusions: TH represents a promising therapeutic target that may better capture the full burden of inflammation in CD than mucosal endpoints alone. Future efforts should focus on harmonizing imaging criteria and determining whether targeting TH can translate into meaningful disease modification and improved long-term outcomes. Full article

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15 pages, 1503 KB

Open AccessArticle

Endoscopic Activity Prediction in Ulcerative Colitis Using Hemogram-Derived Inflammatory Indices: Impact of Azathioprine Use on Diagnostic Performance

by Muhammed Kaya, Gökhan Evren, İbrahim Durak, Tolga Düzenli, Hüseyin Köseoğlu and Mustafa Sadeçolak

J. Clin. Med. 2026, 15(16), 6464; https://doi.org/10.3390/jcm15166464 - 21 Aug 2026

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Abstract

Objective: In ulcerative colitis (UC), endoscopic assessment remains central to disease monitoring, but repeated colonoscopy is invasive and resource-intensive. This study evaluated the association and discriminatory performance of the systemic immune–inflammation index (SII; platelet × neutrophil/lymphocyte) and the hemoglobin–albumin–lymphocyte–platelet (HALP; hemoglobin × albumin [...] Read more.

Objective: In ulcerative colitis (UC), endoscopic assessment remains central to disease monitoring, but repeated colonoscopy is invasive and resource-intensive. This study evaluated the association and discriminatory performance of the systemic immune–inflammation index (SII; platelet × neutrophil/lymphocyte) and the hemoglobin–albumin–lymphocyte–platelet (HALP; hemoglobin × albumin × lymphocyte/platelet) score for endoscopic activity in UC and explored whether azathioprine use modified these associations. Methods: Among 428 retrospectively reviewed patients with UC, 218 met the inclusion criteria. Mayo-defined activity (endoscopic score ≥ 2) and Rachmilewitz EAI-defined activity (score ≥ 4) were analyzed as separate outcomes. Laboratory parameters were compared between active disease and remission groups. Receiver operating characteristic (ROC) analyses, multivariable logistic regression, sensitivity analyses accounting for disease duration and treatment category, and azathioprine interaction analyses were performed. Results: According to the Mayo and Rachmilewitz EAI definitions, 80 (36.7%) and 150 (68.8%) patients, respectively, had active disease. For Mayo-defined activity, CRP showed the highest discrimination (AUC = 0.720), followed by SII (AUC = 0.692), whereas HALP showed limited discrimination (AUC = 0.598). In the primary multivariable Mayo model, CRP, SII, younger age, and male sex were independently associated with activity, whereas HALP and azathioprine use were not. Adding SII to CRP produced only a small numerical increase in AUC (0.720 to 0.752), and adding HALP produced essentially no further change. No significant interaction between azathioprine use and SII or HALP was identified. Conclusion: SII was associated with endoscopic activity but showed only modest discriminatory performance, while HALP had limited discriminatory and independent predictive value. CRP remained the strongest individual biomarker. SII and HALP should therefore be interpreted as adjunctive inflammatory indices rather than substitutes for established biomarkers or endoscopic assessment. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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16 pages, 2697 KB

Open AccessArticle

Endocytoscopic Classification Is Associated with Mucosal miR-192-5p Downregulation and CXCL2 Expression in Ulcerative Colitis: An Exploratory Study

by Shungo Kanetsuki, Hiroki Kurumi, Tsutomu Kanda, Natsuki Hayashi, Takeshi Hashimoto, Ryohei Ogihara, Yu Kamitani, Yuichiro Ikebuchi, Koichiro Kawaguchi, Kazuo Yashima and Hajime Isomoto

Diagnostics 2026, 16(15), 2449; https://doi.org/10.3390/diagnostics16152449 - 3 Aug 2026

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Abstract

Background/Objectives: Ultra-high-magnification endoscopy (Endocyto) visualizes microscopic mucosal structures and has been proposed as a tool for assessing mucosal inflammation. We previously developed an endocytoscopic classification system (EC-A to EC-D) for grading the severity of inflammation. In this study, we investigated the relationship [...] Read more.

Background/Objectives: Ultra-high-magnification endoscopy (Endocyto) visualizes microscopic mucosal structures and has been proposed as a tool for assessing mucosal inflammation. We previously developed an endocytoscopic classification system (EC-A to EC-D) for grading the severity of inflammation. In this study, we investigated the relationship between endocytoscopic classification and microRNA (miRNA) expression in 36 patients with ulcerative colitis (UC). Methods: This cross-sectional study was conducted in two phases at two institutions. In the first phase, microarray analysis was performed on biopsy samples from patients with UC and healthy controls enrolled at Nagasaki University Hospital. In the second phase, 36 patients with UC who underwent total colonoscopy via Endocyto at Tottori University Hospital were included, and selected miRNAs were analyzed via quantitative polymerase chain reaction. Results: Differentially expressed miRNAs were identified, and four (miR-141-5p, miR-192-5p, miR-194-5p, and miR-215-5p) were downregulated in inflammatory areas. Notably, miR-192-5p expression was markedly lower in the EC-B and EC-C+D groups than in the EC-A group. Furthermore, expression of CXC motif ligand 2 (CXCL2), a pro-inflammatory chemokine, was upregulated in inflammatory tissues and negatively correlated with miR-192-5p expression. Conclusions: These results indicate that reduced miR-192-5p expression is inversely associated with CXCL2 expression and that, among the miRNAs examined, miR-192-5p downregulation most consistently corresponded to the endocytoscopic classification. Our findings suggest that Endocyto may serve as a real-time, in vivo adjunct for a histology-like assessment of mucosal inflammation; its clinical utility requires prospective validation. Full article

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42 pages, 18496 KB

Open AccessArticle

Chemical Profiling of Commiphora gileadensis, Salsola incanescens, and Savignya parviflora and Their Protective Effects in an Acute Rat Model of Ulcerative Colitis

by Fawaz K. Alanazi, Nashwa Hashad, Asmaa A. Ahmed, Elsayed K. El-Sayed, Yara E. Mansour, Mohamed I. S. Abdelhady, Eman G. Haggag and Fatma M. Abdel Bar

Pharmaceuticals 2026, 19(8), 1178; https://doi.org/10.3390/ph19081178 - 27 Jul 2026

Viewed by 447

Abstract

Background/Objectives: Ulcerative colitis (UC) is a relapsing colonic disorder in which persistent immune-mediated inflammation is accompanied by oxidative imbalance and deterioration of the protective intestinal mucosal barrier. Due to disease complexity and limitations of current therapies, alternative and adjunctive treatments are needed. [...] Read more.

Background/Objectives: Ulcerative colitis (UC) is a relapsing colonic disorder in which persistent immune-mediated inflammation is accompanied by oxidative imbalance and deterioration of the protective intestinal mucosal barrier. Due to disease complexity and limitations of current therapies, alternative and adjunctive treatments are needed. This study investigated the phytochemical profiles and anti-UC activities of Commiphora gileadensis, Salsola incanescens, and Savignya parviflora. Methods: The methanolic extracts of aerial parts (AMEs) were characterized using LC-MS/MS and evaluated for their protective effects against acetic acid (AA)-induced UC in female Sprague Dawley rats. Animals were treated orally once daily for 14 days with extract doses of 250 and 500 mg/kg prior to colitis induction. In vitro anti-inflammatory and NO scavenging activities were also evaluated. Molecular docking was performed to explore the potential mechanisms of action by predicting the interactions of key compounds with COX-1 and 2 and the TLR4/MD-2 complex. Results: LC-MS/MS analysis revealed flavonoid-rich extracts with characteristic metabolites, including triterpenes in C. gileadensis, phenolic amides in S. incanescens, and amino acids in S. parviflora. C. gileadensis exhibited the strongest in vitro anti-inflammatory activity, showing marked suppression of interleukin-6 and tumor necrosis factor-α production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages, selective COX-2 inhibition, and potent NO scavenging activity comparable to celecoxib. The extracts significantly attenuated AA-induced colonic injury in a dose-dependent manner. C. gileadensis at 500 mg/kg exhibited the highest protective efficacy by reducing disease activity index, colonic edema, oxidative stress, and inflammatory mediators, while restoring mucosal architecture. It downregulated TLR4 and attenuated NF-κB-dependent inflammatory and iNOS pathways. Histopathological examination and mucin expression results were consistent with these findings. Molecular docking was utilized as a hypothesis-generating tool to provide an in silico insight into the anti-inflammatory activity of C. gileadensis, suggesting potential multi-target interactions with COX-1, COX-2, and the TLR4/MD-2 complex, likely attributable to its unique triterpenoid and flavonoid constituents. Conclusions: C. gileadensis emerged as the most promising extract for UC management, exhibiting marked antioxidant and anti-inflammatory effects. Further mechanistic, pharmacokinetic, and clinical investigations are required to establish its translational potential for the treatment of UC. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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15 pages, 3454 KB

Open AccessReview

The Emerging Role of Ultrasonography in Ulcerative Colitis

by Anna Testa, Livio Bonacci, Antonio Rispo, Alessia Dalila Guarino, Olga Maria Nardone, Felice Imoletti, Flavia Palumbo, Martina Petolicchio, Francesca D’Orsi and Fabiana Castiglione

Diagnostics 2026, 16(15), 2319; https://doi.org/10.3390/diagnostics16152319 - 24 Jul 2026

Viewed by 654

Abstract

Background/Objectives: Intestinal ultrasound (IUS) is a non-invasive and reliable technique for the assessment and monitoring of ulcerative colitis (UC) in the era of tight disease control, although its accuracy is reduced for rectal evaluation. Its utility is further enhanced by transperineal ultrasonography [...] Read more.

Background/Objectives: Intestinal ultrasound (IUS) is a non-invasive and reliable technique for the assessment and monitoring of ulcerative colitis (UC) in the era of tight disease control, although its accuracy is reduced for rectal evaluation. Its utility is further enhanced by transperineal ultrasonography (TPUS) and has also been demonstrated in patients with acute severe ulcerative colitis (ASUC) and in the postoperative assessment of ileal pouch function. Methods: We performed a narrative review on the emerging applications of IUS in UC with the findings obtained from research on the abovementioned topic on the PubMed database. Our search terms were “inflammatory bowel disease”, “IBD”, “ulcerative colitis”, “intestinal ultrasound”, “TPUS”, “HH”, “point of care ultrasound”, and “bowel ultrasound”. Results: IUS can assess UC disease activity and could be used in monitoring treatment response. Rectal assessment may represent a limitation of standard IUS, but the use of TPUS can overcome this issue, thus also allowing pouch evaluation after surgery. Another emerging application of IUS is in ASUC, a potential life-threatening condition where complete endoscopic assessment may not be feasible, so IUS could be a valid technique to assess disease extension and, in the first days, response to rescue therapy. Moreover, the use of hand-held sonography (HH), with portable ultrasonographic devices allowing point-of-care, bedside examination in various settings, is rising, showing accuracy comparable to standard techniques. Conclusions: IUS is emerging as a valuable tool in the management of patients with UC and could be an attractive option for point-of-care evaluation in the diagnosis, monitoring and prediction of long-term disease course, even after surgery or in the setting of ASUC. Complementary tools, such as TPUS and hand-held ultrasound, represent promising technologies, requiring prospective multicenter validation before routine clinical implementation. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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18 pages, 2933 KB

Open AccessSystematic Review

Comparing the Efficacy of Advanced Interleukin Inhibitors for Crohn’s Disease: A Systematic Review and Network Meta-Analysis

by Qiuyue Zhang, Mengqi Luo and Yufang Wang

J. Clin. Med. 2026, 15(14), 5593; https://doi.org/10.3390/jcm15145593 - 16 Jul 2026

Viewed by 605

Abstract

Background: IL-23p19 inhibitors have recently gained approval for treating moderate-to-severe Crohn’s disease (CD). Nevertheless, their comparative efficacy relative to each other and to the IL-12/23 inhibitor ustekinumab (UST) is controversial. Therefore, this study evaluated risankizumab (RZB), mirikizumab (MRK), guselkumab (GUS), and UST for [...] Read more.

Background: IL-23p19 inhibitors have recently gained approval for treating moderate-to-severe Crohn’s disease (CD). Nevertheless, their comparative efficacy relative to each other and to the IL-12/23 inhibitor ustekinumab (UST) is controversial. Therefore, this study evaluated risankizumab (RZB), mirikizumab (MRK), guselkumab (GUS), and UST for inducing and maintaining clinical and endoscopic remission in the moderate-to-severe CD population. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched until 4 November 2025. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. The clinical and endoscopic remission/response during induction and maintenance phases was examined through a frequentist network meta-analysis (NMA). Subgroup analyses were carried out in the biologic-naïve population and those with prior biologic failure. Results: This NMA included 15 RCTs within 11 studies with 7747 patients. Relative to UST, IL-23p19 inhibitors demonstrated superior efficacy during induction and maintenance therapy. For clinical remission during the induction, GUS < 600 mg displayed significantly greater efficacy than UST 6 mg/kg (RR: 1.34 [95% CI: 1.06–1.70]). For endoscopic remission during the induction, both RZB > 600 mg (RR: 1.66 [95% CI: 1.14–2.41]) and RZB ≤ 600 mg (RR: 1.65 [95% CI: 1.21–2.25]) were superior to UST 6 mg/kg. During maintenance therapy, 200 mg GUS achieved a higher rate of endoscopic remission than UST (RR: 2.04 [95% CI: 1.09–3.49]). According to the SUCRA rankings, IL-23p19 inhibitors, particularly GUS and RZB, consistently ranked above UST across all evaluated outcomes. Conclusions: IL-23p19 inhibitors demonstrated superior efficacy in comparison to the IL-12/23 inhibitor UST in the moderate-to-severe CD population. Further high-quality, long-term, multicenter RCTs and real-world studies could confirm these findings. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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20 pages, 6533 KB

Open AccessArticle

Lactobacillus rhamnosus GG Alleviates Colitis by SLC5A12-Mediated Th17/Treg Cell Balance in Mice

by Yiling Zhang, Xianghong He, Qian Zhao, Qiming Duan, Heping Li, Rui Qin, Weifang Zuo, Kunhong Xie and Bo Han

Nutrients 2026, 18(11), 1724; https://doi.org/10.3390/nu18111724 - 28 May 2026

Cited by 1 | Viewed by 610

Abstract

Background/Objectives: Lactobacillus rhamnosus GG (LGG) is one of the most widely utilized probiotic strains with a variety of biological functions including prevention and treatment of gastro-intestinal infections and regulation of immune responses. Methods: Here, we explored the role of LGG in [...] Read more.

Background/Objectives: Lactobacillus rhamnosus GG (LGG) is one of the most widely utilized probiotic strains with a variety of biological functions including prevention and treatment of gastro-intestinal infections and regulation of immune responses. Methods: Here, we explored the role of LGG in regulating the differentiation of naïve CD4⁺ T cells and its effect on alleviating the dextran sulfate sodium (DSS)-induced colitis in mice. Results: In vitro, we showed that LGG-derived metabolites not only promoted the differentiation of naive CD4⁺ T cells into T-helper 17 cells (Th17 cells), but also selectively upregulated the expression of lactate-specific transporter solute carrier family 5 member 12 (SLC5A12). Interestingly, we manipulated a CD4⁺ T cell-monocytes co-culture and found that heated LGG-loaded monocytes modulate naive CD4⁺ T cells to differentiate preferentially into Treg cells rather than Th17 cells. To explain the above-mentioned contradiction, we used an experimental colitis model and found that LGG administration alleviated the DSS-induced colitis in mice, as indicated by decreases in weight loss and disease activity index. Moreover, SLC5A12 blockade (using a specific antibody) further reduced the colonic histological inflammatory score and decreased secretion of proinflammatory cytokines such as IFN-γ, IL-6, IL-17F, and IL-21. Notably, SLC5A12 blockade abolished the LGG-induced differentiation of the IL-17⁺CD4⁺ T (Th17) cells but significantly increased the frequency of Foxp3⁺CD4⁺ T (Treg) cells in the colonic lamina propria. Furthermore, a higher intracellular lactate concentration was observed in the colonic CD4⁺ T cells isolated from the LGG-treated colitic mice compared with other groups. Additionally, we also found elevated levels of oxidative stress indicators such as MDA and H₂O₂, as well as excessive reactive oxygen species (ROS) in colonic tissue of DSS-treated only mice, while LGG can scavenge ROS by inducing nuclear factor-erythroid 2-related factor 2 (Nrf2) expression in enterocytes. Conclusions: Altogether, these results indicate that LGG might alleviate preclinical colitis by modulating the Th17/Treg balance, and SLC5A12 blockade appears to enhance the anti-inflammatory properties of LGG. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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26 pages, 802 KB

Open AccessReview

Intestinal Barrier: Mechanisms of Disruption and Strategies for Restoration in Ulcerative Colitis

by Mei-Na Wang, Chuan-Guo Liu, Jia Pan, Xiao-Gang Pang and Hui-Min Liu

Gastrointest. Disord. 2026, 8(2), 24; https://doi.org/10.3390/gidisord8020024 - 17 May 2026

Viewed by 2389

Abstract

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Intestinal barrier impairment represents a core pathogenic mechanism and a key therapeutic target for achieving mucosal healing and sustained remission. Methods: This narrative review summarizes intestinal barrier structure, disruption mechanisms, [...] Read more.

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease. Intestinal barrier impairment represents a core pathogenic mechanism and a key therapeutic target for achieving mucosal healing and sustained remission. Methods: This narrative review summarizes intestinal barrier structure, disruption mechanisms, barrier-targeted therapies, and non-invasive monitoring approaches. A reproducible literature search was conducted in PubMed, Web of Science, and ClinicalTrials.gov from 2015 to 2026. Results: Barrier disruption in UC involves genetic susceptibility, proinflammatory cytokines, zonulin-mediated tight junction injury, gut microbiota dysbiosis, decreased short-chain fatty acids and secondary bile acids, impaired autophagy, and an abnormal mucin 2 (MUC2)-dependent mucus layer. Validated non-invasive monitoring tools include fecal calprotectin/lactoferrin, intestinal ultrasound, diffusion-weighted magnetic resonance imaging (MRI), and intravoxel incoherent motion (IVIM). Emerging therapies focus on tight junction stabilization, epithelial regeneration, autophagy regulation, MUC2 restoration, and microbiota modulation. Conclusions: Intestinal barrier dysfunction drives the initiation and progression of UC. Barrier-based monitoring and targeted repair strategies improve UC management. Future studies should develop personalized therapies, precise microbiota engineering, and multi-dimensional digital evaluation systems. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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20 pages, 773 KB

Open AccessSystematic Review

Benefits of Surgical Management in Ileocecal Crohn’s Disease: A Review of the Past Decade (2020–2026)

by Ion Balint, Roxana Zaharie, Vălean Dan, Emil Moiș, Călin Popa, Andra Ciocan, Nadim Al-Hajjar and Florin Zaharie

Medicina 2026, 62(5), 949; https://doi.org/10.3390/medicina62050949 - 13 May 2026

Viewed by 648

Abstract

Background and Objectives: The management of localized ileocecal Crohn’s disease (CD) is undergoing a significant paradigm shift from traditional “step-up” medical escalation toward proactive early surgical intervention. With the evolution of surgical therapies as well as various minimally invasive procedures, as well [...] Read more.

Background and Objectives: The management of localized ileocecal Crohn’s disease (CD) is undergoing a significant paradigm shift from traditional “step-up” medical escalation toward proactive early surgical intervention. With the evolution of surgical therapies as well as various minimally invasive procedures, as well as a better understanding of inflammatory bowel diseases, surgery is playing a more important role in the treatment of inflammatory bowel disease. One of the most common occurrences in Crohn’s disease, the ileocecal localization can present with a lot of dilemmas regarding the optimal treatment in both adult patients and pediatric patients alike. One of the biggest challenges remains the decision between early surgery and continuous biological treatment, which can prove a challenge from multiple standpoints ranging from cost-efficiency to recurrence rate. This review highlights the latest changes in surgical management in ileocecal Crohn’s disease, focusing primarily on the anastomotic type, comparison with biological therapy, early aggressive surgery and pediatric surgery. Materials andMethods: After respecting the review criteria, 16 articles were included in our study, which emphasize the importance and the recent trends in the surgical management of the ileocecal disease. Results: All 16 articles met criteria for good quality, suggesting a low risk of bias, focusing primarily on early surgery, the role of Kono-S anastomosis as well as pediatric considerations. Conclusions: While the choice of the Kono-S anastomosis remains debatable, significant progress has been made in terms of early surgery which improves the long-term outcomes in patients while minimizing the risk of morbidity and mortality. Full article

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10 pages, 490 KB

Open AccessBrief Report

Bacterial Gastrointestinal Infections in Pediatric Inflammatory Bowel Disease (PIBD)—A Single-Center Experience of Epidemiology, Management, and Outcome

by Raffaela Miriam Planka, Almuthe Christine Hauer, Sebastian Bauchinger and Benno Kohlmaier

Diagnostics 2026, 16(9), 1411; https://doi.org/10.3390/diagnostics16091411 - 6 May 2026

Viewed by 526

Abstract

Background: Due to dysbiosis, intestinal barrier dysfunction, and immunosuppressive therapy, pediatric inflammatory bowel disease (PIBD) patients are more susceptible to infections. However, data on bacterial gastrointestinal (GI) infections in this population are scarce, and no guidelines explicitly address immunosuppressive therapy management during such [...] Read more.

Background: Due to dysbiosis, intestinal barrier dysfunction, and immunosuppressive therapy, pediatric inflammatory bowel disease (PIBD) patients are more susceptible to infections. However, data on bacterial gastrointestinal (GI) infections in this population are scarce, and no guidelines explicitly address immunosuppressive therapy management during such infections. This single-center study aims to address these knowledge gaps. Methods: A retrospective study of bacterial GI infections was conducted in PIBD patients aged 0–18 years, treated between 2011 and 2021 at the Department of Pediatrics and Adolescent Medicine, Medical University of Graz. Data to assess the study endpoints were extracted from the hospital information system. Results: A total of 139 PIBD patients were screened for bacterial GI infections. The mean follow-up time was 49 months (standard deviation ±33) and the total follow-up time amounted to approximately 473 person-years. Fourteen patients developed infections, with three experiencing them twice, resulting in 17 cases of infection. Most infections were caused by opportunistic bacteria, and 10 infections were treated with antibiotics (11 antibiotic prescriptions in total). At infection onset, 12 patients were on (combined) immunosuppressive therapy, including corticosteroids (3 patients), immunomodulators (9 patients), and/or biologics (3 patients). Six infections required escalation of immunosuppressive therapy due to increased PIBD activity. Hospitalization was required in five cases, and one Clostridioides difficile infection progressed to sepsis, necessitating intensive care unit admission. This corresponds to an incidence of three infections (95% confidence interval 1.75–4.80) and 0.2 severe infections per 100 person-years (95% confidence interval 0.01–1.11). Conclusions: The incidence of bacterial GI infections was 3 per 100 person-years (95% confidence interval: 1.75–4.80), with most cases being clinically mild. Clostridioides difficile was the most common pathogen. Immunosuppressive therapy was generally continued or intensified, when necessary, while antibiotic therapy was administered as indicated. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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12 pages, 2906 KB

Open AccessArticle

Terminal Ileal Ulcers: Endoscopic Predictors for the Later Development of Crohn’s Disease

by Weiqi Zhang, Kun Zhang, Yang Yang, Haibin Dong, Shan Xie, Xiaojuan Guo, Bo Jiang, Yutang Ren and Shiming Zhou

Diagnostics 2026, 16(9), 1339; https://doi.org/10.3390/diagnostics16091339 - 29 Apr 2026

Viewed by 1375

Abstract

Background: Terminal ileal ulcers (TIUs) are frequently identified during colonoscopy but are often attributed to nonspecific etiologies, potentially delaying the diagnosis of Crohn’s disease (CD). This study aimed to evaluate the utility of TIU as an early diagnostic marker and to determine whether [...] Read more.

Background: Terminal ileal ulcers (TIUs) are frequently identified during colonoscopy but are often attributed to nonspecific etiologies, potentially delaying the diagnosis of Crohn’s disease (CD). This study aimed to evaluate the utility of TIU as an early diagnostic marker and to determine whether diagnosis at the isolated TIU stage impacts long-term surgical outcomes. Methods: In this single-center, retrospective cohort study, consecutive adult patients with TIU detected via colonoscopy over a 10-year period were analyzed. Patients were stratified into CD-TIU and non-CD-TIU cohorts based on longitudinal follow-up. Clinical, endoscopic, and laboratory parameters were compared. Long-term surgical outcomes of patients diagnosed at the isolated TIU stage (Montreal classification L1) were compared with those of patients with established ileocolonic disease (Montreal classification L3). Results: Of the 66 patients included in the final analysis, 18 (27.3%) were ultimately diagnosed with CD. Specific endoscopic features—including longitudinal or fissuring ulcers (50.0% vs. 6.3%, p < 0.001), ileocecal valve deformity (50.0% vs. 18.8%, p = 0.011), and increased ulcer dimensions (9.11 mm vs. 4.60 mm, p = 0.002)—were significantly associated with a CD diagnosis. Notably, patients diagnosed at the TIU stage (CD-L1) exhibited a significantly lower surgical rate compared to those with established ileocolonic disease (CD-L3) (5.6% vs. 70.2%, p < 0.001). Conclusions: TIU, particularly when characterized by longitudinal morphology or ileocecal valve involvement, constitutes a critical early manifestation of CD. Diagnosis at the isolated TIU stage is associated with a lower long-term surgical risk compared to established ileocolonic disease, likely reflecting the influence of disease phenotype. These findings underscore the imperative for meticulous endoscopic evaluation to identify early-stage disease. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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17 pages, 2567 KB

Open AccessArticle

The Assessment of Multidimensional Clinical, Biological and Patient-Reported Outcomes to Evaluate the Efficacy of Add-On Lactobacillus rhamnosus GG Supplementation in Mild Ulcerative Colitis: A Randomized Pilot Trial

by Paola Maragno, Chiara Amoroso, Simone Conforti, Marco Michelon, Ivanna Honcharyuk, Clorinda Ciafardini, Daniele Noviello, Francesco Strati, Flavio Caprioli, Federica Facciotti and Maurizio Vecchi

Nutrients 2026, 18(9), 1329; https://doi.org/10.3390/nu18091329 - 23 Apr 2026

Viewed by 1185

Abstract

Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints [...] Read more.

Background: Ulcerative colitis (UC) is a multifactorial disease characterized by aberrant mucosal immune activation in response to intestinal dysbiosis. Contemporary management strategies aim to target inflammation and microbiome alterations while reducing relapse risk. A multidimensional assessment integrating clinical, inflammatory, immune, and microbial endpoints may better capture therapeutic effects beyond symptom control. Aims: To evaluate whether supplementation with Lactobacillus rhamnosus GG co-formulated with vitamin D3 (Dicoflor IBD Immuno) as an adjunct to optimized mesalamine (5-ASA) is associated with coordinated changes across clinical and biological domains in mild-to-moderate UC, using a multidimensional assessment framework. Methods: This single-center, randomized, double-blind, placebo-controlled pilot trial was conducted at Fondazione Ca’ Granda IRCCS Policlinico di Milano between May 2022 and May 2024. Thirty-six patients with mild-to-moderate UC receiving optimized 5-ASA were randomized to LGG+VitD3 (ALD3) or placebo (AP) for 4 weeks. Clinical activity, health-related quality of life (HRQoL), fecal calprotectin, peripheral immune cell subsets, and gut microbiota composition were assessed at baseline and week 4. Results: Both 5-ASA-LGG+VitD3 (ALD3)- and 5-ASA-placebo (AP)-treated patients showed significant improvement in clinical activity and HRQoL, without between-group differences. A higher proportion of clinical responders was observed in the ALD3 group, although this was not statistically significant. LGG+VitD3-supplemented patients showed reduced fecal calprotectin levels and increased frequencies of IL-22-producing CD4⁺ T cells. Microbiome analysis revealed enrichment of short-chain fatty acid-producing taxa, including Coprococcus and Fusicatenibacter, in ALD3-treated patients. Conclusions: In patients with mild UC receiving optimized 5-ASA, LGG+VitD3 supplementation does not improve short-term clinical outcomes beyond placebo but is associated with favorable modulation of inflammatory, immune, and microbial parameters, supporting the relevance of multidimensional biological endpoints in adjunctive UC management. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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35 pages, 1053 KB

Open AccessReview

Biosensor-Based Detection of Calprotectin and Lactoferrin as Neutrophil-Derived Markers of Inflammatory Bowel Diseases: From Molecular Pathophysiology to Point-of-Care Platforms

by Nikita Sitkov, Andrey Ryabko, Sergei Ivanov, Yuri Cheburkin, Alexey Kolobov, Diana Khasanova, Vladimir Nikolaev, Dmitrii Kaplun and Kamil Gareev

Int. J. Mol. Sci. 2026, 27(6), 2692; https://doi.org/10.3390/ijms27062692 - 16 Mar 2026

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Abstract

Inflammatory bowel diseases (IBD) are chronic, relapsing, immune-mediated disorders that require regular and preferably noninvasive monitoring of inflammatory activity. Fecal biomarkers of neutrophilic inflammation, namely calprotectin and lactoferrin, therefore represent key analytical targets for diagnosis and longitudinal disease management. Despite their widespread clinical [...] Read more.

Inflammatory bowel diseases (IBD) are chronic, relapsing, immune-mediated disorders that require regular and preferably noninvasive monitoring of inflammatory activity. Fecal biomarkers of neutrophilic inflammation, namely calprotectin and lactoferrin, therefore represent key analytical targets for diagnosis and longitudinal disease management. Despite their widespread clinical use, existing publications predominantly address either their clinical relevance or individual technical solutions, without establishing a comprehensive engineering-translational framework for their biosensor-based implementation. This review bridges this gap by providing an integrative analysis of the molecular and biological nature of calprotectin and lactoferrin, the mechanisms underlying their appearance in fecal matrices, and the analytical constraints that directly influence the design of hybrid point-of-care (PoC) biosensor systems. We systematically compare major biosensing platforms, emphasizing sensor architecture, signal transduction mechanisms, and sample preparation strategies as critical determinants of sensitivity, selectivity, reproducibility, and clinical relevance. The novelty of this review lies in combining the pathophysiological context of neutrophilic inflammation with physicochemical and technological aspects of biosensor development, enabling a transition from laboratory prototypes to evaluation of real translational readiness. The practical significance resides in establishing a methodological basis for rational design of next-generation hybrid-integrated biosensor systems and outlining perspectives for digital analytics and artificial intelligence in clinically interpretable IBD monitoring. Full article

(This article belongs to the Topic Advances in Comprehensive Management Strategies for Inflammatory Bowel Disease)

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