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.

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.

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.

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.

The successful encapsulation of CGA within FTCLP was confirmed through examination using electron microscopy, fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The in vitro release characteristics of FTCLP were evaluated using the dialysis bag membrane method. Meanwhile, a dextran sulfate sodium (DSS) -induced colitis model was employed to investigate the anti-inflammatory effect of FTCLP and its mechanism.

The FTCLP exhibited an encapsulation efficiency (EE) of 84.85 ± 1.20% and a drug loading (DL) of 11.67 ± 0.04%. The particle size of FTCLP was determined to be 150.63 ± 0.71 nm, with a polydispersity index (PDI) of 0.198 ± 0.02 and a zeta potential of 2.61 ± 0.38 mV. The in vitro release profile followed the Higuchi model, indicating sustained-release characteristics. The in vivo study demonstrated that FTCLP treatment was effective in improving the symptoms of DSS-induced inflammatory response, as evidenced by mitigation of weight loss, reduction in the disease activity index (DAI) score, restoration of colon length, and attenuation of colon tissue damage. Furthermore, the levels of pro-inflammatory cytokines, including interferon-gamma (INF-γ), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), were markedly diminished in both the serum and colon tissue. FTCLP was also observed to suppress the expression of INF-γ, IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65, while concomitantly upregulating the expression of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3). Besides, the administration of FTCLP was found to result in an increase in the abundance of Lactobacillaceae and Peptostreptococcaceae, while decreasing the abundance of Bacteroidaceae, Rikenellaceae, and Helicobacteraceae.

Following encapsulation of CGA within liposomes, FTCLP revealed favorable stability and sustained release properties, and enhanced the anti-inflammatory effects by modulating multiple inflammation-related biomarkers. FTCLP has the potential to be a safe and effective drug for targeted therapy of colitis.

The strong connection between gut microbes and human health has been confirmed by an increasing number of studies. Although probiotics have been found to relieve ulcerative colitis, the mechanism varies by the species involved. In this study, the physiological, immune and pathological factors of mice were measured and shotgun metagenomic sequencing was conducted to investigate the potential mechanisms in preventing ulcerative colitis.

The results demonstrated that ingestion of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 significantly alleviated ulcerative colitis induced by dextran sulfate sodium (DSS), as evidenced by the increase in body weight, food intake, water intake and colon length as well as the decrease in disease activity index, histopathological score and inflammatory factor. Both strains not only improved intestinal mucosa by increasing mucin-2 and zonula occludens-1, but also improved the immune system response by elevating interleukin-10 levels and decreasing the levels of interleukin-1β, interleukin-6, tumor necrosis factor-α and interferon-γ. Moreover, L. fermentum GLF-217 and L. plantarum FLP-215 play a role in preventing DSS-induced colitis by regulating the structure of gut microbiota and promoting the formation of short-chain fatty acids.

This study may provide a reference for the prevention strategy of ulcerative colitis. © 2024 Society of Chemical Industry.

The infliximab biosimilar CT-P13 was the first biosimilar drug targeting tumor necrosis factor-α. However, its efficacy and safety in real-world clinical situations have remained insufficient. Therefore, we aimed to verify the efficacy and safety of CT-P13 in bio-naïve patients with Crohn's disease.

This retrospective multicenter study compared the remission rate at week 54 between patients with Crohn's disease who were treated with originator infliximab or CT-P13. Endoscopic and laboratory findings were assessed in both groups. A total of 184 (156 originator and 28 CT-P13) patients were analyzed. Of these, 138 originator users and 19 biosimilar users completed 54-week administration.

The clinical remission rates in patients taking originator infliximab of CT-P13 at week 54 were 92.5 % and 100 %, respectively. The endoscopic scores of each group significantly decreased from baseline at week 54 in both groups, and the mucosal healing rate at week 54 was 53 % and 64 %, respectively. Laboratory data including C-reactive protein, serum albumin, and hemoglobin significantly improved from baseline to week 14 and 54 in both groups. Adverse events were observed more frequently in the CT-P13 group (25 % vs. 4.5 %, p = 0.0015), but severe adverse events were rare in both groups.

The efficacy and safety of CT-P13 were comparable with those of originator infliximab in bio-naïve patients with Crohn's disease evaluated by clinical, endoscopic, and laboratory findings. This study establishes the needed groundwork for the development of a strategy for treatment with biologics in patients with Crohn's disease.

Vedolizumab is a treatment option for ulcerative colitis but data on predictors of treatment response remain insufficient to establish personalized treatment strategies. We aimed to investigate the real-world effectiveness of vedolizumab in adult patients with ulcerative colitis and explore factors involved in predicting treatment response. This single-center, single-arm, prospective observational study included 26 patients with clinically active ulcerative colitis patients' characteristics at baseline, epidemiological information, existing treatment, clinical activity index score, endoscopic score, and blood test data were collected. Serum levels of tumor necrosis factors alpha, interferon gamma, interleukin-4, interleukin-6, interleukin-10, interleukin-17, soluble mucosal addressin cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1 were measured. Patient characteristics in the remission and non-remission groups were compared based on these parameters. Clinical remission at 6 weeks of treatment occurred in 9 (35%) of the 26 patients. At 14 weeks, clinical remission was observed in 11 patients (42%). There were no significant differences pertaining to age, sex, duration of disease, extent of disease, steroid resistance, or prior treatment with biological agents among the two groups after 14 weeks of treatment. Hemoglobin ≥ 11.5 g/dL (odds ratio, 15.0; 95% confidence interval, 1.50-149; P=0.014) and soluble mucosal addressin cell adhesion molecule 1 ≥ 765 pg/mL (odds ratio, 17.3; 95% confidence interval, 2.36-127; P=0.004) were significant factors. In conclusion, hemoglobin and serum soluble mucosal addressin cell adhesion molecule 1 levels are factors correlated with the therapeutic efficacy of vedolizumab.

Close monitoring of disease activity in IBD patients is essential to avoid long term complications. Although endoscopic assessment is the ideal monitoring tool, the usage of noninvasive biomarkers is more practical and patient friendly. We aimed to study the performance of Interleukin-6(IL-6) and Serum Amyloid A(SAA) as serum biomarkers in assessment of the disease activity of IBD patients in correlation to C-reactive protein (CRP), Fecal Calprotectin (FC) and endoscopic indices.

83 IBD (26 CD and 57 UC) patients on stable treatment regimen were recruited. Serum markers included CRP, CBC, IL-6, SAA were analyzed, together with FC. These markers were compared with the endoscopic and clinical disease parameters. Harvey-Bradshaw Index (HBI) and the Simple Clinical Colitis Activity Index (SCCAI) were used to assess clinical activity in CD and UC patients, respectively. Endoscopic activity was recorded using the Simple Endoscopic Score (SES) for Crohn's disease or the Mayo Endoscopic Score (MES) for ulcerative colitis.

In prediction of disease activity, IL-6, SAA and CRP demonstrated good area under receiver operating characteristics (AUC) (>0.7), with FC being the best (0.94) for endoscopically active disease (P < 0.01). Combining FC and IL-6 or SAA improved its discriminative accuracy with an AUC (∼0.96).

FC most accurately predicts endoscopic disease activity in IBD patients, in comparison to other studied serological biomarkers. The serum IL-6 and SAA are potential predictors of endoscopic disease activity, and they might be valuable for assessment of disease activity. Finally, a composite score of FC and SAA or IL-6 can increased its diagnostic accuracy.

Designing highly efficient orally administrated nanotherapeutics with specific inflammatory site-targeting functions in the gastrointestinal tract for ulcerative colitis (UC) management is a noteworthy challenge. Here, we focused on exploring a specific targeting oral nanotherapy, serving as "one stone," for the directed localization of inflammation and the regulation of redox homeostasis, thereby achieving effects against "two birds" for UC treatment. Our designed nanotherapeutic agent OPNs@LMWH (oxidation-sensitive ε-polylysine nanoparticles at low-molecular weight heparin) exhibited specific active targeting effects and therapeutic efficacy simultaneously. Our results indicate that OPNs@LMWH had high integrin αM-mediated immune cellular uptake efficiency and preferentially accumulated in inflamed tissues. We also confirmed its effectiveness in the treatment experiment of colitis in mice by ameliorating oxidative stress and inhibiting the activation of inflammation-associated signaling pathways while simultaneously bolstering the protective mechanisms of the colonic epithelium. Overall, these findings underscore the compelling dual functionalities of OPNs@LMWH, which enable effective oral delivery to inflamed sites, thereby facilitating precise UC management.

Inflammatory bowel disease (IBD) is a chronic relapsing disease of the gastrointestinal (GI) system that includes two groups, Crohn's disease (CD) and ulcerative colitis (UC). To cope with these two classes of IBD, the investigation of pathogenic mechanisms and the discovery of new diagnostic and therapeutic approaches are crucial. Long non-coding RNAs (lncRNAs) which are non-coding RNAs with a length of longer than 200 nucleotides have indicated significant association with the pathology of IBD and strong potential to be used as accurate biomarkers in diagnosing and predicting responses to the IBD treatment. In the current review, we aim to investigate the role of lncRNAs in the pathology and development of IBD. We first describe recent advances in research on dysregulated lncRNAs in the pathogenesis of IBD from the perspective of epithelial barrier function, intestinal immunity, mitochondrial function, and intestinal autophagy. Then, we highlight the possible translational role of lncRNAs as therapeutic targets, diagnostic biomarkers, and predictors of therapeutic response in colon tissues and plasma samples. Finally, we discuss the potential of extracellular vesicles and their lncRNA cargo in the pathophysiology, diagnosis, and treatment of IBD.

Ulcerative colitis (UC) is a chronic inflammation of the gastrointestinal tract and is characterized by alternating periods of inflammation and remission. Although UC incidence is lower in Taiwan than in Western countries, its impact remains considerable, demanding updated guidelines for addressing local healthcare challenges and patient needs. The revised guidelines employ international standards and recent research, emphasizing practical implementation within the Taiwanese healthcare system. Since the inception of the guidelines in 2017, the Taiwan Society of Inflammatory Bowel Disease has acknowledged the need for ongoing revisions to incorporate emerging therapeutic options and evolving disease management practices. This updated guideline aims to align UC management with local contexts, ensuring comprehensive and context-specific recommendations, thereby raising the standard of care for UC patients in Taiwan. By adapting and optimizing international protocols for local relevance, these efforts seek to enhance health outcomes for patients with UC.