Ulcerative colitis (UC) is a chronic inflammatory bowel disease for which remission is dependent on corticosteroid (CS) treatment. The diversity of disease pathophysiology necessitates optimal case-specific treatment selection. This study aimed to identify prognostic factors for refractory UC using a machine learning model based on nationwide registry data.

The study included 4003 patients with UC with a Mayo score of ≥3 at the time of registration who had been using CS since their entry out of 79,096 newly registered UC cases in a nationwide registry from April 2003 to March 2012 (before the widespread use of biologic agents in Japan) with 3-year data. A pointwise linear (PWL) model was used for machine learning.

A PWL model, which was developed to predict long-term remission (lasting >3 years), had an area-under-the-curve (AUC), precision rate, recall rate, and F-value of 0.774, 0.55, 0.70, 0.62, respectively, in the test dataset from the time of registration to 2 years later. Furthermore, the presence of pseudopolyps at the time of registration was significantly and negatively correlated with remission, highlighting its importance as a prognostic factor.

In this study, we constructed a highly accurate prognosis prediction model for UC, in which inflammation persists for an extensive period, by training a machine learning model for long-term disease progression. The results showed that machine learning can be used to determine the factors affecting remission during the treatment of refractory UC.

SiniSan (SNS), a traditional formula from the Treatise on Typhoid Fever, has been shown in modern clinical practice to effectively treat both ulcerative colitis (UC) and depression, although the underlying mechanisms remain incompletely understood.

This study employed UPLC-Q-Orbitrap-MS, network pharmacology, molecular docking, and experimental validation to investigate SNS's mechanism in treating UC with comorbid depression.

UPLC-Q-Orbitrap-MS, in conjunction with network pharmacology and molecular docking, identified active constituents and potential targets of SNS. A UC model induced by a 3 % dextran sulfate sodium (DSS) solution was used for experimental validation. Therapeutic efficacy was assessed through behavioral tests, ELISA, routine blood tests, histopathology, immunofluorescence, Western blot, and qRT-PCR.

SNS alleviated weight loss and inflammation in DSS-induced colitis in mice while exhibiting antidepressant effects in the open field test, forced swim test, and tail suspension test. Furthermore, SNS improved intestinal mucosal barrier function and restored hippocampal blood-brain barrier integrity. It inhibited microglial proliferation and neuroinflammation in the Hippocampus Cornu Ammonis 1 and dentate gyrus regions. Mechanistic analysis revealed that SNS mediates its effects on UC by modulating targets in the PI3K/AKT signaling pathway.

SNS ameliorates UC with comorbid depression by restoring the integrity of both the intestinal mucosal barrier and the blood-brain barrier, alleviating DSS-induced colitis and neuroinflammation.

Medication adherence is critical in 5-aminosalicylate therapy for patients with ulcerative colitis. Patients with a history of previous medication self-discontinuation may continue to have low adherence due to the influence of inappropriate disease awareness. This study aimed to determine the association between the history of previous medication self-discontinuation and current adherence to 5-aminosalicylates in patients with ulcerative colitis.

This cross-sectional study was conducted in Japan from 2021 to 2024. A self-administered questionnaire was used in 228 patients with ulcerative colitis who were taking 5-aminosalicylates. We defined adherence as consumption of ≥ 80% of the prescribed dose. Patients with a history of previous medication self-discontinuation were defined as having discontinued medication at least once in the past by their own judgment. The current adherence rate to 5-aminosalicylates in this study was 92.9% (212/228). The proportion of patients with a history of previous medication self-discontinuation was 7.8% (18/228). History of previous medication self-discontinuation (p < 0.001), younger age (p < 0.001), and once-daily 5-aminosalicylates regimen (p < 0.001) were inversely associated with current adherence to 5-aminosalicylates.

History of previous medication self-discontinuation was inversely associated with current adherence to 5-aminosalicylates among patients with ulcerative colitis. The results of this study suggest that determining the history of previous medication self-discontinuation may be a valuable tool in assessing current adherence to 5-aminosalicylates, which can be cumbersome.

Little research has explored in-depth qualitative opinions on anticipated public views of Inflammatory Bowel Disease (IBD) among those with the condition, and the potential impact of these views on wellbeing. This study explored the perceptions and reactions anticipated by those with IBD from the public (RQ1), and the impact these anticipated perceptions have on participants' physical and psychological health, and their quality of life (RQ2).

Twenty participants (aged 18-56 years) were recruited via Crohn's and Colitis Australia and online IBD support forums. Individual, semi-structured interviews were conducted with participants. To avoid researcher bias, two independent data coders conducted thematic analysis to identify themes and subthemes.

The themes identified by both coders were further examined and reported. Four themes were identified: (1) poor public awareness of IBD; (2) difficulties with disclosure; (3) emotional and social public reactions; and lastly, (4) 'self-exclusion'. Most participants indicated that their physical health and quality of life are not impacted by their anticipated views, however, some participants reported that their psychological health is impacted.

This study uncovered the adverse impact of anticipated public views on psychological health. Regarding study implications, self-excluding behaviours should be routinely assessed in clinical practice.

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition marked by persistent intestinal inflammation of unknown etiology. Disease onset involves genetic predisposition and environmental factors that disrupt the intestinal immune homeostasis. The intestinal microbiome and immune response play pivotal roles in disease progression. Advances in molecular therapies and early interventions have reduced surgery rates; however, colorectal cancer (CRC) remains a significant concern, driven by chronic inflammation. In UC, the risk of UC-associated neoplasia (UCAN) increases with disease duration, while CD patients face elevated risks of small intestine, anal fistula, and anal canal cancers. Endoscopic surveillance is advised for UCAN, but optimal screening intervals remain undefined, and no established guidelines exist for CD-associated cancers. UCAN morphology often complicates detection due to its flat, inflammation-blended appearance, which differs pathologically from sporadic CRC (sCRC). UCAN is frequently surrounded by dysplasia, with p53 mutations evident at the dysplasia stage. IBD-associated gastrointestinal cancers exemplify inflammation-driven carcinogenesis with distinct molecular mechanisms from the adenoma-carcinoma sequence. This review explores the epidemiology, risk factors, clinical and pathological features, current surveillance practices, and molecular pathways underlying inflammation-associated cancers in IBD.

Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that increase the risk of cardiovascular diseases (CVD). Patients with inflammatory bowel disease (IBD) may be at higher risk of developing MetS due to chronic inflammation, altered adipokine profiles, and the effects of corticosteroid treatment. However, the prevalence of MetS in IBD patients remains inconsistent across studies. This meta-analysis aims to estimate the prevalence of MetS in IBD patients and compare its occurrence between Crohn's disease (CD) and ulcerative colitis (UC).

A systematic search was conducted across PubMed, Scopus, Embase, and Web of Science from their inception up to January 19, 2025. Eligible observational studies reporting MetS prevalence in IBD patients were included. Meta-analysis was performed using a random-effects model, with heterogeneity assessed via the I² statistic. Comprehensive Meta-Analysis (CMA) software, version 4.0 was used for analysis.

The pooled prevalence of MetS in IBD patients was 21.8% (95% CI: 14.3-31.6%). The prevalence was higher in UC patients (32.7%, 95% CI: 16.0-55.5%) compared to CD patients (14.1%, 95% CI: 8.6-22.3%). Patients with UC had significantly higher odds of MetS than those with CD (OR = 1.38, 95% CI: 1.03-1.85, P = 0.02). Additionally, IBD patients with MetS were significantly older than those without (MD: 9.89, 95% CI: 5.12-14.67, P < 0.01).

In summary, this meta-analysis reveals a notable prevalence of MetS among patients with IBD, particularly in those with UC, where the prevalence is higher than in CD. The analysis also shows that IBD patients with MetS tend to be older, suggesting age as a contributing factor. These findings underscore the need for routine metabolic screening in IBD care, especially in UC and elderly patients.

Endoscopic balloon dilation (EBD) is an effective treatment for intestinal strictures in Crohn's disease (CD). However, restenosis often occurs and requires repeat EBD or surgery. Previous studies have seldom examined restenosis with respect to stricture diameter, leaving the factors contributing to post-EBD restenosis unclear. Our retrospective study indicated that complete mucosal healing significantly reduces restenosis after EBD in CD-related small intestinal strictures. This prospective study aimed to validate these findings by accurately measuring stricture diameters in patients with CD.

We conducted a single-center prospective study of patients with CD and small intestinal strictures. The patients underwent an EBD session between June 2022 and December 2023. Stricture diameters were measured using a calibrated small-caliber-tip transparent hood. Multivariate analysis was performed to identify factors influencing stricture progression.

This study included 41 patients (33 men). The number of strictures detected between sessions increased from 159 to 170. The average diameter of all strictures and the narrowest stricture per patient showed slight increases. However, 73% of patients experienced stricture progression. The presence of ulcers between sessions was identified as a significant risk factor for stricture progression (odds ratio 7.59, p = 0.031). Patients achieving complete mucosal healing demonstrated a significant increase in the narrowest stricture diameter (+1.5 mm, p = 0.00089).

Complete mucosal healing is crucial for preventing stricture progression after EBD in patients with CD-related small intestinal strictures.

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gastrointestinal tract with limited treatment options. This study investigates the preventive effects of fermented Kamut wheat enzyme (FKW) diet on the progression of dextran sulfate sodium (DSS)-induced colitis in mice, with a focus on gut microbiota modulation and inflammatory cytokine regulation. Female C57BL/6J mice were divided into groups and fed a diet consisting of either a FKW diet (containing 39.80% FKW) or a control diet under 1.25% and 2.50% DSS conditions. The FKW diet was formulated based on the AIN-93G standard rodent formula, with the FKW diet providing comparable amounts of total proteins, crude lipids, and dietary fibers as the control diet. The FKW diet effectively mitigated the progression of colitis, as evidenced by improvements in key indicators such as dietary intake, body weight, colon length, stool consistency, and bleeding, particularly in the 1.25% DSS group. Histopathological analysis revealed preservation of colonic architecture and reduced mucosal damage in the FKW group. The diet also resulted in a significant reduction in pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and IFN-γ) and myeloperoxidase (MPO) levels, coupled with an increase in anti-inflammatory IL-10. Gut microbiota analysis showed increased abundance of beneficial bacteria such as Muribaculaceae, Lachnospiraceae NK4A136 and Bacteroides acidifaciens and decreased pathogenic bacteria like Escherichia/Shigella and Bilophila. These findings underscore the potential of FKW as a preventive dietary intervention for mitigating the progression of colitis, emphasizing the role of gut microbiota in supporting intestinal health. These results highlight FKW's potential to reduce the risk of colitis development, providing a foundation for future research into its preventive applications.

Emerging evidence indicates that chloride channels (ClCs) significantly affect the pathogenesis of inflammatory bowel disease (IBD) through their regulatory roles in mast cell function and epithelial integrity. IBD, encompassing conditions such as Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract, where channels influence immune responses, fluid balance, and cellular signalling pathways essential for maintaining mucosal homeostasis. This review examines the specific roles of ClC in mast cells, focussing on the regulation of mast cell activation, degranulation, cytokine release, and immune cell recruitment in inflamed tissues. Key channels, including Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and ClC-2, are discussed in detail because of their involvement in maintaining intestinal epithelial barrier function, a critical factor disrupted in IBD. For example, CFTR facilitates chloride ion transport across epithelial cells, which is essential for mucosal hydration and maintenance of the intestinal barrier. Reduced CFTR function can compromise this barrier, permitting microbial antigens to penetrate the underlying tissues and triggering excessive immune responses. ClC-2, another chloride channel expressed in mast cells and epithelial cells, supports tight junction integrity, contributes to barrier function, and reduces intestinal permeability. Dysregulation of these channels is linked to altered mast cell activity and excessive release of pro-inflammatory mediators, exacerbating IBD symptoms, such as diarrhoea, abdominal pain, and tissue damage. Here, we review recent pharmacological strategies targeting ClC, including CFTR potentiators and ClC-2 activators, which show the potential to mitigate inflammatory responses. Additionally, experimental approaches for selective modulation of chloride channels in mast cells have been explored. Although targeting ClC offers promising therapeutic avenues, challenges remain in achieving specificity and minimizing side effects. This review highlights the therapeutic potential of Cl channel modulation in mast cells as a novel approach for IBD treatment, aiming to reduce inflammation and restore intestinal homeostasis in affected patients.

Inflammatory bowel disease is a type of chronic gastrointestinal inflammatory disease. The chronic nature of the disease, the severity of its symptoms, and its unpredictability make it comparable to cancers regarding both its influence on quality of life and the direct and indirect health costs. The impact of inflammatory bowel disease on daily life is well documented; however, despite the notable increase in the incidence of inflammatory bowel disease in recent years, the international literature still does not adequately take into account the perspective of patients and how they experience the disease in their daily lives. With Cohen's phenomenology method, we investigate the lived experience of people suffering from inflammatory bowel disease. Our sample included 21 participants with an average age of 47 years. Three main themes and related subthemes emerged: A "deep life change" with the subtheme of "self-isolation," being "invisibly sick," and "receiving the diagnosis" with the subtheme of "trust in health professionals." Understanding the lived experiences of people living with inflammatory bowel disease will aid in the development of educational programs and effective interventions.

Objectives: This bibliometric analysis investigates recent research trends in biologics and small molecules for treating inflammatory bowel disease (IBD) based on literature from the past decade. Methods: This cross-sectional study involved analyzing data retrieved from the Web of Science Core Collection (WoSCC) database to examine the evolution and thematic trends of biological agents and small-molecular drugs for IBD conducted between 1 January 2014, and 20 September 2024. VOSviewer software was utilized to assess co-authorship, co-occurrence, co-citation, and network visualization, followed by a further discussion on significant sub-themes. Results: From 2014 to 20 September 2024, the annual number of global publications increased by 23%, reflecting an acceleration in research activity. The journal "Inflammatory Bowel Diseases" published the highest number of manuscripts (579 publications) and garnered the most citations (13,632 citations), followed by the "Journal of Crohn's & Colitis" (480 publications) and "Alimentary Pharmacology & Therapeutics" (250 publications). The United States led in productivity with 1943 publications and 66,320 citations, with UC San Diego (291) and authors Sandborn and Vermeire (180) topping the list. The co-occurrence cluster analysis of the top 100 keywords resulted in the formation of six distinct clusters: Disease Mechanisms, Drug Development, Surgical Interventions, Therapeutic Drug Monitoring (TDM), Immunological Targets, and Emerging Therapies. Burst terms (TNF-α inhibitors, JAK inhibitors, and trough-level optimization) highlight trends toward personalized biologics and small-molecule regimens. Conclusions: The bibliometric analysis indicates that IBD therapeutic research and clinical applications focus on biologics and small molecules, with research trends leaning toward precise therapy conversion or the combination in non-responders. Future work will assess monotherapy, the combination, and conversion therapies and investigate new drugs targeting inflammatory pathways.

Crohn's disease (CD) is an incurable inflammatory condition that often requires multiple surgeries, negatively impacting quality of life. As such, treatment strategies that aim to prevent damage to the bowel and reduce the burden of surgeries for patients with CD are important. This retrospective, long-term, observational study investigated whether tumor necrosis factor inhibitor (TNFi) treatment was associated with decreased rates of abdominal surgery in Japanese patients with CD.

Patients were divided into two groups based on prior TNFi therapy (TNFi-treated and TNFi-untreated). Outcomes assessed included surgery rate, cumulative surgery-free survival rate, and time to surgery. For surgery rate, treatment groups were compared through estimation of an odds ratio (OR) with 95% confidence intervals (CIs). Cumulative surgery-free survival rate and time to surgery was calculated using Kaplan-Meier methodology and compared using log-rank tests. The primary analysis compared outcomes between the TNFi-treated and TNFi-untreated groups. Subgroup analyses compared outcomes between two subgroups of the TNFi-treated group (infliximab-treated vs. adalimumab-treated) and the TNFi-untreated group.

Overall, 124 patients with CD were included in the analysis (TNFi-treated: N = 86; TNFi-untreated: N = 38). Of those patients who received TNFi treatment, 62 received infliximab and 24 received adalimumab. The median (range) observation period in the TNFi-treated and TNFi-untreated groups was 4.62 (0.41-13.75) years and 8.13 (0.08-30.25) years, respectively. Median time to surgery was 3 years in the TNFi-untreated group and 6.58 years in the TNFi-treated group. A significantly lower proportion of patients in the TNFi-treated group required surgery (3/86) compared with those in the TNFi-untreated group (17/38; OR [CI]: 0.0446 [0.0120-0.1667]; P < 0.0001). Cumulative surgery-free survival rates were significantly higher in the TNFi-treated group versus the TNFi-untreated group (P < 0.0001). Compared with the TNFi-untreated group, the proportion of patients who required surgery was significantly lower with both infliximab (1/62; OR [CI]: 0.0203 [0.0025-0.1616]; P = 0.0002) and adalimumab (2/24; OR [CI]: 0.1123 [0.0231-0.5466]; P = 0.0068). Cumulative surgery-free survival rates were significantly higher in the infliximab-treated group versus the TNFi-untreated group (P < 0.0001).

Introduction of TNFis for the treatment of CD may lead to a reduction in surgery rates and prolong time to surgery.

Achievement of endoscopic healing (EH) is significant in the clinical practice of inflammatory bowel disease as it is correlated with improved prognosis. Existing biomarkers, including C-reactive protein (CRP), have relatively low accuracy for predicting EH, especially in small intestinal lesions in Crohn's disease (CD); thus, noninvasive and more accurate biomarkers are required. Leucine-rich alpha-2 glycoprotein (LRG), a 50-kD protein, is produced under inflammatory conditions and has been reported to be useful in assessing disease activity in inflammatory bowel disease. However, the usefulness of LRG in small intestinal lesions in CD remains inconclusive.

To determine the usefulness of LRG for EH in small bowel lesions in CD and compare it with CRP.

This study included 133 consecutive patients with CD who underwent balloon-assisted enteroscopy between June 2021 and March 2024 at Shiga University of Medical Science Hospital (Otsu, Japan). We retrospectively analyzed endoscopic scores in each of the ileum and colon and four markers including LRG, CRP, albumin, and Harvey-Bradshaw index (HBI). Spearman's rank correlation coefficient and receiver operating characteristic analysis were performed.

Either active ileal or colonic lesions exhibited significant differences in LRG, CRP, albumin, and HBI compared with EH. CRP, albumin, and HBI showed a worse correlation with endoscopic activity in the ileum than that in the colon; however, LRG did not show a worse correlation (colon, r = 0.5218; ileum, r = 0.5602). Receiver operating characteristic analysis revealed that LRG for EH in the ileum and colon had the same cutoff values of 12.4 μg/mL. Comparing the areas under the curve of LRG and CRP for predicting EH in the ileum revealed a significantly higher areas under the curve of LRG (95% confidence interval, 0.017-0.194; P = 0.024), whereas the two showed no significant difference in the colon.

LRG is a useful biomarker in assessing the endoscopic activity of CD and is more useful than CRP in the small intestine.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, significantly increases the risk of colon adenocarcinoma (COAD). Disulfidptosis, a novel form of programmed cell death, has been implicated in various diseases, including UC. This study investigates the expression of disulfidptosis-related genes, particularly CD2AP and MYH10, in UC and COAD. Through analysis of public datasets, we found MYH10 significantly upregulated and CD2AP downregulated in UC compared to healthy controls, with consistent patterns in COAD. Immune infiltration analysis revealed correlations between these genes and specific immune cell types, suggesting their roles in immune modulation. Molecular docking showed strong binding affinities of UC drugs such as budesonide and sulfasalazine with CD2AP and MYH10. Connectivity Map analysis identified additional drug candidates, including simvastatin and mephenytoin, which may be repurposed for UC and COAD therapy. These findings suggest disulfidptosis-related genes as potential biomarkers and therapeutic targets, linking chronic inflammation to cancer progression.

Patients with a long history of ulcerative colitis (UC) are at risk of developing a serious complication known as UC-associated neoplasia (UCAN). Because the treatment strategy for UCAN greatly differs from that for sporadic tumors, UCAN needs to be distinguished from sporadic tumors. This article provides an overview of the current status and future challenges regarding the surveillance colonoscopy (SC) and endoscopic submucosal dissection (ESD) of neoplastic lesions in patients with UC.

To reduce the risk of associated mortality, the current guidelines recommend initiating SC using chromoendoscopy with high-definition colonoscopy 8-10 years after the confirmation of a UC diagnosis. However, the endoscopic diagnosis of UCAN is occasionally challenging and requires a stepwise approach using multiple endoscopic modalities. The worldwide consensus is that a diagnosis of high-grade dysplasia or higher is an indication for proctocolectomy. Although the management of low-grade dysplasia (LGD) remains controversial, the SCENIC consensus statement recommends the complete removal of "endoscopically resectable" LGD, followed by monitoring. ESD was developed in Japan, allows for the removal of complex gastrointestinal lesions, facilitates the treatment of LGD, and enables precise pathological evaluations to differentiate between UCAN and sporadic tumors and to determine the grade of dysplasia in UCAN. Close endoscopic surveillance should follow complete endoscopic resection. A Japanese expert consensus meeting recommended the performance of follow-up SC 6-12 months after complete resection with ESD.

The roles of ESD for UCAN are to treat LGD and to enable the histopathological examination of complete excisional biopsy specimens to differentiate between UCAN and sporadic tumors and grade the dysplasia of UCAN. In future, prospective cohort studies are needed to better assess the clinical outcomes of ESD in patients with UC.

Adalimumab (ADM) therapy is effective for inflammatory bowel disease (IBD), but a significant number of IBD patients lose response to ADM. Thus, it is crucial to devise methods to enhance ADM's effectiveness. This study introduces a strategy to predict individual serum concentrations and therapeutic effects to optimize ADM therapy for IBD during the induction phase.

We predicted the individual serum concentration and therapeutic effect of ADM during the induction phase based on pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated using the empirical Bayesian method. We then examined whether the predicted therapeutic effect, defined as clinical remission or treatment failure, matched the observed effect.

Data were obtained from 11 IBD patients. The therapeutic effect during maintenance therapy was successfully predicted at 40 of 47 time points. Moreover, the predicted effects at each patient's final time point matched the observed effects in 9 of the 11 patients.

This is the inaugural report predicting the individual serum concentration and therapeutic effect of ADM using the Bayesian method and PK/PD modelling during the induction phase. This strategy may aid in optimizing ADM therapy for IBD.

Whether Astragalus membranaceus is an effective drug in the treatment of ulcerative colitis (UC) is unknown and how it exhibits activity in UC is unclear.

TCMSP, GeneCards, String, and DAVID databases were used to screen target genes in PPI network and we performed GO and KEGG pathway enrichment analysis. Molecular docking and animal experiments were performed. The body weight and disease activity index (DAI) of mice were recorded. ELISA kits were used to detect the levels of CAT, SOD, MDA and IL-6, IL-10, TNF-α in the blood of mice. Western blot kits were utilized to measure the expression of MAPK14, RB1, MAPK1, JUN, ATK1, and IL2 proteins.

The active components of Astragalus membranaceus mainly include 7-O-methylisomucronulatol, quercetin, kaempferol, formononetin and isrhamnetin. Astragalus membranaceus may inhibit the expression of TNF-α, IL-6, MDA, while promoting the expression of CAT, SOD, and IL-10. The expression levels of MAPK14, RB1, MAPK1, JUN and ATK1 proteins were significantly decreased while IL2 protein increased after administration of Astragalus membranaceus.

Astragalus membranaceus may be an effective drug in the treatment of UC by acting on targets with anti-UC effect via its antioxidant action and by regulating the balance of pro-inflammatory and anti-inflammatory factors.

Pediatric inflammatory bowel disease (PIBD), including Crohn's disease and ulcerative colitis, has emerged as a significant global health challenge with rising incidence rates. Unlike adult inflammatory bowel disease, PIBD presents complexities, including growth impairment, nutritional deficiencies, and psychosocial challenges that necessitate tailored management strategies. This article reviews current diagnostic and emerging treatment strategies to highlight the evolution from traditional therapies such as aminosalicylates, corticosteroids, and immunomodulators to advanced biologic agents like infliximab and adalimumab. Emerging biological therapies, including vedolizumab and ustekinumab, show promise, while novel small molecule therapies such as Janus kinase (JAK) inhibitors are under investigation for potential use in the pediatric population. Supportive treatments, including exclusive enteral nutrition, modified diets, and probiotics, play a critical role in comprehensive disease management. Stem cell therapy and fecal microbiota transplant represent innovative approaches still under clinical evaluation. The review underscores the significance of holistic care, incorporating mind-body interventions and psychosocial support to improve patient quality of life. Key challenges persist, such as infection risks associated with long-term biological therapy use, gaps in pediatric-specific guidelines, and the limited inclusion of children in clinical trials. Future recommendations emphasize the importance of structured transition programs bridging pediatric and adult care, regular updates to clinical guidelines, and the integration of precision medicine to personalize treatment plans. Continued research and collaboration are essential for advancing the understanding and management of PIBD, ensuring that pediatric patients benefit from the most effective, evidence-based care available.

This study aimed to evaluate the risk of tumor formation with infliximab or azathioprine monotherapy versus their combination, using the FDA Adverse Event Reporting System (FAERS) database.

Data were extracted from the FAERS database for patients treated with infliximab, azathioprine, and combination therapy from Q1 2004 to Q2 2024. Signal mining employed methods such as Reported Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multiple Gamma-Poisson Scaling Assessment (MGPSA) and Bayesian Confidence Interval Progressive Neural Network (BCPNN).

Our analysis of the FAERS database revealed that the highest number of reported cases involved skin-related tumors, both individually and in combination. In terms of sex, the risk of cancer was higher in men compared to women in the infliximab-only and combination groups; however, no sex difference was observed in the azathioprine-only group. Regarding age, we noted an increasing incidence of adverse tumor events in middle-aged and elderly individuals compared to minors, except in the azathioprine group, where age was not identified as an independent risk factor. Additionally, body weight was not found to be an independent risk factor in any of the three medication groups. After controlling for age, sex, and body weight, combination therapy did not increase the risk of tumor development compared to the azathioprine group alone. In contrast, for patients using infliximab alone, combination therapy not only did not elevate the risk of tumor development but also appeared to reduce it. The results of the Weber distribution suggest a random failure-type profile for the infliximab and azathioprine-only group, while an early failure-type profile was observed for the combination therapy. Furthermore, we analyzed the median time to onset and cumulative incidence rates, revealing no significant differences in median time to tumor onset or cumulative incidence rates between the combination therapy and the single agent.

After adjusting for age, sex, and body weight, combination therapy did not significantly increase tumor development risk compared to the azathioprine-only group. Additionally, in patients on infliximab monotherapy, combination therapy appeared to reduce the risk of tumor development.

There is insufficient evidence comparing the outcomes of tacrolimus-based remission induction therapy with infliximab in refractory ulcerative colitis (UC) and evidence regarding optimal strategies after tacrolimus-based remission induction therapy. We conducted a multi-institutional retrospective study of patients with UC treated with tacrolimus or infliximab between January 2010 and March 2019. The proportion of clinical remission at week 8 and cumulative colectomy-free rate were examined using propensity score matching analysis. The predictors for colectomy after tacrolimus induction were also investigated. Ninety patients in the tacrolimus group and 151 in the infliximab group were enrolled. The proportion of patients in clinical remission at week 8 was 65.2% in the matched tacrolimus group and 37.3% in the matched infliximab group (P = 0.0016), and the long-term colectomy-free rate was lower in the matched tacrolimus group than in the matched infliximab group (P = 0.0003). After clinical remission with tacrolimus, a serum albumin level of ≤ 3.5 g/dL at week 8 was extracted as a factor predicting colectomy (area under the curve: 0.94). Tacrolimus showed a higher remission induction effect for UC compared to infliximab. However, a high rate of colectomy after transition to maintenance treatment was found to be a concern for tacrolimus therapy.

The inflammatory bowel diseases (IBD) occur in genetically susceptible individuals that mount inappropriate immune responses to their microbiota leading to chronic intestinal inflammation. The natural history of IBD progression begins with early subclinical stages of disease that occur before clinical diagnosis. Improved understanding of those early subclinical stages could lead to new or improved strategies for IBD diagnosis, prognostication, or prevention. Here, we review our current understanding of the early subclinical stages of IBD in humans including studies from first-degree relatives of patients with IBD and members of the general population who go on to develop IBD. We also discuss representative mouse models of IBD that can be used to investigate disease dynamics and host-microbiota relationships during these early stages. In particular, we underscore how mouse models of IBD that develop disease later in life with variable penetrance may present valuable opportunities to discern early subclinical mechanisms of disease before histological inflammation and other severe symptoms become apparent.

Differentiating between Crohn's disease (CD) and gastrointestinal tuberculosis (GITB) is challenging. We aimed to evaluate the clinical applicability of an artificial intelligence (AI) model for this purpose.

The AI model was developed and assessed using an internal dataset comprising 1,132 colonoscopy images of CD and 1,045 colonoscopy images of GITB at a tertiary referral center. Its stand-alone performance was further evaluated in an external dataset comprising 67 colonoscopy images of 17 CD patients and 63 colonoscopy images of 14 GITB patients from other institutions. Additionally, a crossover trial involving three expert endoscopists and three trainee endoscopists compared AI-assisted and unassisted human interpretations.

In the internal dataset, the sensitivity, specificity, and accuracy of the AI model in distinguishing between CD and GITB were 95.3%, 100.0%, and 97.7%, respectively, with an area under the ROC curve of 0.997. In the external dataset, the AI model exhibited a sensitivity, specificity, and accuracy of 77.8%, 85.1%, and 81.5%, respectively, with an area under the ROC curve of 0.877. In the human endoscopist trial, AI assistance increased the pooled accuracy of the six endoscopists from 86.2% to 88.8% (P = 0.010). While AI did not significantly enhance diagnostic accuracy for the experts (96.7% with AI vs 95.6% without, P = 0.360), it significantly improved accuracy for the trainees (81.0% vs 76.7%, P = 0.002).

This AI model shows potential in aiding the accurate differential diagnosis between CD and GITB, particularly benefiting less experienced endoscopists.

Lysophpsphospholipids (LPLs) are lipid mediators involved in various physiological functions. In daily diets, people consume large amounts of various lipids, including LPLs. Exogenous dietary LPLs initially affect epithelial cells and, finally, the entire colon and may be linked to the onset and prevention of colonic diseases, including inflammatory bowel disease. However, the effects of exogenous LPLs on epithelial cells remain poorly understood. In this study, we used HT-29, a human colon cancer-derived epithelial cell, to evaluate the effects of LPLs on epithelial cells under normal and inflammatory states. In the absence of lipopolysaccharide (LPS), several LPLs decreased interleukin-8 (IL-8) secretion from HT-29 cells in the following order of potency based on the reduction ratio at the highest concentration: lysophosphatidylglycerol > lysophosphatidylcholine > lysophosphatidyletanolamine > lysophosphatidylserine. In the presence of LPS, only lysophosphatidylinositol (LPI) decreased the IL-8 secretion induced by LPS. Focusing on the G protein-coupled receptors (GPCRs) that LPI acts on, PSN375963 and AS1269574, GPR119 agonists, decreased the IL-8 secretion induced by LPS. It is speculated that IL-8 secretion was reduced by LPI via GPR119 signaling under non-inflammatory conditions. Although the detailed mechanism remains to be elucidated, the findings that LPLs, except for LPI, have inhibitory effects and that LPI has an inhibitory/anti-inflammatory effect on IL-8 secretion will help to elucidate the mechanism on the onset of colonic diseases and the planning of treatment methods in the future.

Ulcerative colitis is a form of chronic inflammatory bowel disease (IBD) marked by ongoing inflammation of the mucosal lining that extends from the rectum to the upper part of the colon. Vitamin D regulates immune responses in several autoimmune and inflammatory diseases, including ulcerative colitis. Therefore, the study aims to investigate the role of vitamin D in the pathogenesis and treatment of ulcerative colitis.

This case-control study included 94 participants who were divided into four groups. Group 1: people with ulcerative colitis who responded to treatment (n = 24). Group 2: family members of patients who responded to treatment and did not have the disease (n = 24). Group 3: People with ulcerative colitis who are resistant to treatment (n = 23). Group 4: family members of treatment-resistant patients who does not have the disease (n = 23). Groups 1 and 3 were considered as patient groups (n = 47) and groups 2 and 4 as control groups (n = 47). Blood samples were taken and analyzed for complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum vitamin D levels.

The mean age of treatment-responsive patients (group 1) was 45.88 ± 18.51 years, while treatment-resistant patients (group 3) averaged 41.30 ± 13.01 (P = 0.33) years. Serum Vitamin D levels were 24.96 ± 9.66 ng/mL in group 1 and 27.70 ± 12.28 ng/mL in group 3, showing no significant correlation with ulcerative colitis (P = 0.41). All groups had a BMI within the normal range, and mean CRP levels varied significantly across groups. Hemoglobin was significantly lower in group 3 compared to group 1 (P = 0.029), but ESR results showed no significant relationship with ulcerative colitis. Vitamin D levels were highest in patients with lower BMI, and no significant relationships were found between Vitamin D and other risk factors, although extensive colitis was associated with higher Vitamin D levels compared to distal colitis.

In this study, there was no significant association between ulcerative colitis and serum levels of vitamin D. However, the small number of patients may limit the conclusions that can be drawn regarding the role of vitamin D in the treatment of ulcerative colitis. Future studies should aim for larger cohorts to provide more definitive insights into this important issue.

Bioactive components from Porphyra tenera (PT) have been reported to confer various health benefits. The role of PT in inflammatory bowel disease (IBD) has not been fully investigated. This study aimed to explore the anti-inflammatory properties of PT on dextran sodium sulfate (DSS)-treated mice. PT supplementation attenuated the severity of colitis in DSS-treated mice, evidenced by the reduction of disease activity index (DAI), restoration of colonic histological damage and suppression of abnormal inflammatory response. Sequencing analysis indicated that intake of PT alleviated DSS-induced gut microbiota dysbiosis, accompanied by reversing the generation of short-chain fatty acids (SCFAs) and bile acids (BAs). Overall, our findings demonstrated that supplementation of PT attenuated the severity of intestinal inflammation and ameliorated gut microbiota dysbiosis in a murine colitis model, which provided a rationale for further application of edible seaweeds for preventing inflammation-related disorders in humans.

Insoluble dietary fiber (IDF) is a crucial component of cereals, and IDF from cereal bran (IDF-CB) has been reported to have multiple biological activities. However, the effect of IDF-CB on chronic colitis remains underexplored. The study aimed to investigate the impact of IDFs from wheat bran (WBIDF), rice bran (RBIDF), millet bran (MBIDF) and oat bran (OBIDF) on chronic colitis induced by dextran sulfate sodium (DSS). Our findings demonstrated that IDFs-CB supplementation mitigated DSS-induced weight loss and reduced lesions in the colon and spleen. Levels of proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α) and oxidative stress markers (MPO, iNOS and MDA)were decreased, and anti-inflammatory cytokine (IL-10) and T-SOD activity were increased after IDF-CB inclusion. Furthermore, IDFs-CB restored intestinal barrier function by regulating gene expression (up-regulated Muc-2, ZO-1 and Occludin, and down-regulated Claudin-1 and Claudin-4). Additionally, we analyzed the gut microbiota and SCFAs composition. WBIDF, MBIDF and OBIDF inhibited the growth of Muribaculaceae_unclassified, Bacteroides and Parasutterella. Conversely, IDFs-CB promoted the growth of Candidatus_Saccharimonas and norank_f__norank_o__Clostridia_UCG-014. Notably, WBIDF enhanced the abundance of Allobaculum, while MBIDF and OBIDF increased the abundance of Lachnospiraceae_NK4A136. Moreover, supplementation with IDFs-CB significantly elevated certain SCFA concentrations-particularly acetic acid and isohexanoic acid. Our results suggested that IDF-CB effectively alleviated DSS-induced chronic colitis; among them，WBIDF exhibited superior efficacy followed by OBIDF，MBIDF，and RBIDF. This study provides a theoretical foundation for dietary recommendations for patients suffering from inflammatory bowel disease.

Inflammatory bowel disease (IBD), comprised of Crohn's disease (CD) and ulcerative colitis (UC), are gut inflammatory diseases that were earlier prevalent in the Western Hemisphere but now are on the rise in the East, with India standing second highest in the incidence rate in the world. Inflammation in IBD is a cause of dysregulated immune response, wherein helper T (Th) cell subsets and their cytokines play a major role in the pathogenesis of IBD. In addition, gut microbiota, environmental factors such as dietary factors and host genetics influence the outcome and severity of IBD. Dysregulation between effector and regulatory T cells drives gut inflammation, as effector T cells like Th1, Th17 and Th9 subsets Th cell lineages were found to be increased in IBD patients. In this review, we attempted to discuss the role of different Th cell subsets together with other T cells like CD8+ T cells, NKT and γδT cells in the outcome of gut inflammation in IBD. We also highlighted the potential therapeutic candidates for IBD.

Background and aim Tacrolimus (tac) is used for induction therapy in refractory and severe ulcerative colitis (UC) cases. The aim of this study was to identify the factors contributing to the induction of remission and to assess the endoscopic or histologic improvement rates following induction of remission by tac. Methods This study examined data from 67 UC patients treated with tac for induction of remission out of 515 patients attending Dokkyo Medical University Hospital. The primary endpoint of the study was the analysis of factors contributing to successful induction of remission treatment with tac. The secondary endpoints were the corticosteroid-free remission rate at 52 weeks after tac induction and the endoscopic and histologic improvement rates following induction of remission. Results Analysis of factors contributing to successful induction of remission by tac showed the Lichtiger index at the beginning of remission induction therapy was 9.5 ± 2.5 for the successful remission group and 11.5 ± 2.4 for the unsuccessful remission group (p = 0.002). The proportions of patients who had used immunomodulators were 13/45 (28.9%) for the successful remission group and 14/22 (63.6%) for the unsuccessful remission group (p = 0.006). The proportions of patients who had used anti-tumor necrosis factor (TNF)α biologics were 4/45 (8.9%) for the successful remission group and 8/22 (36.4%) for the unsuccessful remission group (p = 0.006). Conclusion Patients with UC who are potential candidates for intensification of remission maintenance therapy are good candidates for induction of remission with tac. Moreover, improvement in endoscopic inflammation might be a predictive marker of response to remission induction therapy with tac.

Colorectal neoplasia developing from ulcerative colitis mucosa (CRNUC) can be divided into ulcerative colitis-associated neoplasia (UCAN) and non-UCAN; however, it is often difficult to distinguish UCAN from non-UCAN during a biopsy diagnosis. We investigated whether a genomic analysis could improve the diagnostic accuracy of UCAN using biopsy specimens.

In step 1, 14 CRNUCs were used to examine whether the genomic landscape of biopsy and resection specimens matched. In step 2, we investigated the relationship between the genomic landscapes and the pathological diagnosis of 26 CRNUCs. The cancer genome was analyzed by deep sequencing using a custom panel of 27 genes found to be mutated in our previous CRNUC analysis.

In step 1, of the 27 candidate genes, 14 were mutated. The concordance rate of the pathogenic mutations in these 14 genes between the biopsy and resection specimens was 29% (4/14), while that of the pathogenic mutations in TP53 and KRAS was 79% (11/14). In step 2, the pathological diagnosis of biopsy specimens using only hematoxylin and eosin (HE) staining had a sensitivity of 33% and an accuracy of 38% for UCAN diagnosis. On the other hand, the combination of the HE pathology and p53 immunohistochemical staining had a sensitivity of 73% and an accuracy of 85% for UCAN diagnosis, while the combination of HE staining and a TP53 mutation had a sensitivity of 87% and an accuracy of 88% for UCAN diagnosis.

An evaluation of TP53 mutations in biopsy specimens may be useful for diagnosing UCAN. However, further studies with larger sample sizes are required before this can be applied in clinical practice.

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.

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.

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.

The present study showed that the changes in MAM were characterized by a decrease in mucoprotective bacteria rather than an increase in harmful bacteria.

Autoimmune and autoinflammatory diseases account for more than 80 chronic conditions affecting more than 24 million people in the US. Among these autoinflammatory diseases, noninfectious chronic inflammation of the gastrointestinal (GI) tract causes inflammatory bowel diseases (IBDs), primarily Crohn's and ulcerative colitis (UC). IBD is a complex disease, and one hypothesis is that these are either caused or worsened by compounds produced by bacteria in the gut. While traditional approaches have focused on pan immunosuppressive techniques (e.g., steroids), low remission rates, prolonged illnesses, and an increased frequency of surgical procedures have prompted the search for more targeted and precision therapeutic approaches. IBD is a complex disease resulting from both genetic and environmental factors, but several recent studies have highlighted the potential pivotal contribution of gut microbiota dysbiosis. Gut microbiota are known to modulate the immune status of the gut by producing metabolites that are encoded in biosynthetic gene clusters (BGCs) of the bacterial genome. Here, we show a targeted and high-throughput screening of more than 90 biosynthetic genes in 41 gut anaerobes, through downselection using available bioinformatics tools, targeted gene manipulation in these genetically intractable organisms using the Nanoligomer platform, and identification and synthesis of top microbiome targets as a Nanoligomer BGC cocktail (SB_BGC_CK1, abbreviated as CK1) as a feasible precision therapeutic approach. Further, we used a host-directed immune target screening to identify the NF-κB and NLRP3 cocktail SB_NI_112 (or NI112 for short) as a targeted inflammasome inhibitor. We used these top two microbe- and host-targeted Nanoligomer cocktails in acute and chronic dextran sulfate sodium (DSS) mouse colitis and in TNFΔARE/+ transgenic mice that develop spontaneous Crohn's like ileitis. The mouse microbiome was humanized to replicate that in human IBD through antibiotic treatment, followed by mixed fecal gavage from 10 human donors and spiked with IBD-inducing microbial species. Following colonization, colitis was induced in mice using 1 week of 3% DSS (acute) or 6 weeks of 3 rounds of 2.5% DSS induction for a week followed by 1 week of no DSS (chronic colitis model). Both Nanoligomer cocktails (CK1 and NI112) showed a strong reduction in disease severity, significant improvement in disease histopathology, and profound downregulation of disease biomarkers in colon tissue, as assessed by multiplexed ELISA. Further, we used two different formulations of intraperitoneal injections (IP) and Nanoligomer pills in the chronic DSS colitis model. Although both formulations were highly effective, the oral pill formulation demonstrated a greater reduction in biochemical markers compared to IP. A similar therapeutic effect was observed in the TNFΔARE/+ model. Overall, these results point to the potential for further development and testing of this inflammasome-targeting host-directed therapy (NI112) and more personalized microbiome cocktails (CK1) for patients with recalcitrant IBD.

Psoriasis (PS) and inflammatory bowel disease (IBD) are immune-mediated chronic conditions that share pathophysiological processes, including immune system dysfunction, microbiome dysbiosis, and inflammatory pathways. These pathways result in increased turnover of epithelial cells and compromised barrier function. The assessment of the literature suggests that immunopathogenic mechanisms, such as tumor necrosis factor (TNF)-α signaling and IL-23/IL-17 axis dysregulation, are shared by PS and IBD. Clinical characteristics and diagnostic approaches overlap significantly, and advances in biomarker identification benefit both conditions. Current treatments, namely biologics that target TNF-α, IL-17, and IL-23, show promising results in decreasing inflammation and controlling symptoms. Precision medicine approaches are prioritized in prospective therapeutic procedures to tailor pharmaceuticals based on specific biomarkers, perhaps improving outcomes and minimizing side effects. This study thoroughly examines and evaluates the body of research on PS and IBD. Several papers were examined to compile data on clinical features, diagnosis, therapies, pathophysiology, epidemiology, and potential future therapeutic developments. The selection of articles was based on three methodological qualities: relevance and addition to the knowledge of IBD and PS. The retrieved data were combined to provide a coherent summary of the state of the knowledge and to spot new trends. The overview of the latest studies demonstrates that both PS and IBD share pathophysiological foundations and therapeutic approaches. With a spotlight on particular biomarkers, advances in precision medicine provide a promising path toward enhancing therapeutic effectiveness and minimizing side effects.

Chlorogenic acid (CGA) has been identified to possess salient anti-inflammatory, antioxidant, and anticancer attributes. However, its application is limited by its instability and low bioavailability. Liposomes have been considered effective pharmaceutical delivery vehicles due to their ability to continuously release loaded drugs, improve drug stability, and display good biocompatibility. They can be easily modified by other small molecules to acquire additional biological functions. In this study, we developed and characterized folic acid-TPGS-modified chlorogenic acid liposome (FTCLP) and evaluated its anti-inflammatory activity.