Ulcerative colitis (UC) is a long-term inflammatory bowel disease (IBD) associated with significant morbidity. It is marked by inflammation and damage to the colon's mucosal lining. Studies have shown that NLRP3 inflammasome activation, apoptosis, and impaired autophagy are critical in its pathogenesis. Verapamil, a calcium channel blocker, has been found to inhibit NLRP3 inflammasome activation in various preclinical models. However, the potential influence of verapamil on the TXNIP in UC remains unexplored. This study investigates the effects of verapamil on an UC rat model induced chemically by acetic acid. Verapamil effectively inhibited the TXNIP-NLRP3-caspase-1 axis, reducing inflammasome activation and the release of IL-1β and IL-18. Additionally, verapamil suppressed NFκB, the priming step of NLRP3 activation. The drug enhanced autophagic activity, as indicated by increased expression of LC3-II and Beclin-1, along with reduced LC3-I and mTOR expression. Moreover, it demonstrated anti-apoptotic effects mediated by regulating Bax and cleaved caspase-3. These molecular changes contributed to mucosal healing and improved microscopic and macroscopic outcomes in the colitis model. Furthermore, verapamil improved the colon weight-to-length ratio and disease activity scores and mitigated oxidative stress. As verapamil has been safely used in clinics to treat hypertension, our findings suggest it may be a safe therapeutic option for ameliorating inflammation and apoptosis and activating autophagy in UC pathology. Since hypertension demonstrates a strong association with UC, the use of verapamil merits particular attention in hypertensive patients fighting against IBD.

Inflammatory bowel disease (IBD) subdivides into Crohn disease (CD) and ulcerative colitis (UC), and is characterized by unpredictable periods of inflammation and results in significant patient suffering and even death. Conventional diagnostic methods, for example, colonoscopy, computed tomography, or magnetic resonance imaging, have limitations such as invasiveness, patient discomfort, and limited sensitivity and accuracy. Therefore, we propose ultrasound molecular imaging (USMI) to detect and characterize IBD. First, we evaluated integrin-α v β 3 as a biomarker of IBD in human samples and then used clinically translatable cyclic Arg-Gly-Asp-D-Phe-Lys (cRGDfK)-coupled poly(butyl)cyanoacrylate microbubbles (cRGD-MB) to assess IBD in mice.

Vascular integrin-α v β 3 expression in human colon tissue samples (healthy, CD and UC, n = 10 per group) was analyzed by immunofluorescence staining. In mice, acute colitis was induced by administration of 4% dextran sodium sulfate in drinking water for 5 days. On day 7, USMI with cRGD-MB was performed in colitis (n = 6) and healthy (n = 5) mice. The signal of bound cRGD-MB was assessed by the destruction-replenishment method. Ex vivo analysis of mouse colon tissue was performed to assess the degree of colitis by hematoxylin-eosin staining and the vascular expression of integrin-α v by immunofluorescence.

Human samples showed a significantly higher vascular integrin-α v β 3 expression in CD and UC tissue, when compared with healthy samples ( P < 0.005). In mice, a higher binding of cRGD-MB to inflamed colon was detected by USMI compared with healthy controls ( P < 0.005). Immunofluorescence staining confirmed these findings, showing stronger integrin-α v expression in acute colitis, with a good correlation between USMI signal intensity and integrin-α v expression ( r = 0.8, P = 0.0016).

Integrin-α v β 3 on vessels is a suitable marker for IBD. USMI using cRGD-MB accurately detects this marker and correlates well with histology. These encouraging results support clinical translation of this imaging method as a noninvasive and cost-effective monitoring tool.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract influenced by genetic, environmental, immune, and microbial factors. Reduced gut microbial diversity and elevated proinflammatory bacteria levels in IBD disrupt mucosal immunity, barrier function, and inflammatory pathways. Fecal microbiota transplantation (FMT) is a potential therapy to restore microbial balance. Studies suggest that FMT may induce remission in mild-to-moderate ulcerative colitis but show limited efficacy in Crohn's disease and pouchitis. Donor microbiota colonization correlates with remission, but varied study designs challenge findings. Further research is required to standardize FMT protocols, optimize donor selection, and ensure long-term safety.

Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the intestinal mucosa, with predominant localization in the colon in ulcerative colitis (UC) or affecting the entire length of the gastrointestinal tract in Crohn's disease (CD). Recent advances in the drug development space have been marked by a return to orally administered small molecules with novel mechanisms of action such as Janus kinase inhibitors. Additionally, the prevalence of certain chronic conditions is higher in IBD patients, many of which are treated with orally administered drugs. Given the pathophysiology and localization of IBD, altered drug absorption from the gastrointestinal tract can be expected. This review discusses several physiological differences between the small and large intestine with the potential to influence drug absorption including pathophysiology related alterations associated with IBD. The main physiological parameters which are identified include luminal fluid volume, luminal pH, transit time, bile salt concentration, microbiome, absorptive surface area, permeability and metabolizing enzymes and transporters. Literature regarding these factors in IBD patients is marked with high heterogeneity in reporting of disease severity and location leading to difficulties in interpreting data across different studies. While the influence of most of these factors has been directly assessed in healthy volunteers, this is rarely the case for IBD patients. Furthermore, studies which used PBPK modelling to describe the PK of an orally administered drug in an IBD population and were able to verify their findings using clinical data are critically examined. These models were able to incorporate the pathophysiological changes associated with IBD and partly succeeded in adequately predicting drug absorption in this population. Given the limited amount of PBPK studies performed on a limited number of drugs, the developed models are most likely not suitable to be used as a general PBPK model for the IBD population.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colon. The specific cause of UC is still not fully understood, but this condition is believed to arise from a combination of environmental, genetic, microbial, and immune factors. This study aimed to explore the specific roles of macrophages and fibroblasts in UC pathogenesis, focusing on their interactions and contributions to disease progression.

We utilized single-cell RNA sequencing (scRNA-seq) to analyze macrophages and fibroblasts in peripheral blood and colon biopsy samples from UC patients. Bulk RNA sequencing and spatial transcriptomic data from the Gene Expression Omnibus (GEO) database and flow cytometry and multiplex immunohistochemistry (mIHC) data were used for validation. Statistical analyses were performed to assess the correlation between cell abundance and disease severity.

Macrophages and fibroblasts were identified as key communication hubs in UC; specifically, SPP1 + macrophages and CHI3L1 + fibroblasts were significantly enriched at the sites of inflammation. These cells are strongly correlated with disease severity and orchestrate inflammatory responses within the intestinal immune microenvironment, contributing to UC-associated colorectal cancer.

Our study identified SPP1 + macrophages and CHI3L1 + fibroblasts as key contributors to UC pathogenesis. These cells are enriched in inflammatory sites, are correlated with disease severity, and play a role in UC-associated colorectal cancer, providing new insights into UC mechanisms.

Dysregulation of RNA N6-methyladenosine (m6A) modification in intestinal epithelial cells (IECs) compromises intestinal homeostasis, which is critical for maintaining gastrointestinal functions, immunity, and barrier integrity in inflammatory bowel disease (IBD). Here we explored the role of m6A modification, particularly through methyltransferase like 3 (METTL3), in IBD pathology and the apoptosis of intestinal stem cells (ISCs). Reduced m6A RNA methylation and METTL3 expression were detected in IBD tissues, which correlated with increased ISC apoptosis and spontaneous enteritis in METTL3-deficient models; mechanistically, Mettl3 depletion increased TRADD expression in a m6A-dependent manner, thereby augmenting the TNF-induced apoptosis pathway, whereas pharmacological inhibition of TRADD ameliorated the apoptotic phenotype in METTL3-deficient models and improved survival rates in the enteritis mouse model, suggesting a novel therapeutic avenue for IBD management. Collectively, METTL3-mediated m6A RNA methylation plays a pivotal role in maintaining intestinal homeostasis and is activated in ISCs to mitigate the hyperactivity of endogenous inflammatory signals; by modulating TRADD transcript metabolism, METTL3 limits excessive ISC apoptosis, providing insights into IBD pathogenesis and treatment strategies.

Evidence for a potential link between dietary inflammatory potential and inflammatory bowel disease is limited, and the moderating role of genetic susceptibility remains to be assessed.

To evaluate energy-adjusted dietary inflammatory index (E-DII) for the associations with incident Crohn's disease (CD) and ulcerative colitis (UC) and the role of genetic susceptibility.

A total of 205,706 UK Biobank participants who were aged 39-72 years and had no known CD or UC at baseline (2006-2010) were included. The E-DII score was calculated based on energy-adjusted average intakes of 33 food or nutrient items derived from up to five 24-hour dietary recalls. Multivariable Cox regression models were used estimate hazard ratios (HRs) with 95% confidence interval (CI) for incident CD and UC.

During a median 12.3 years of follow-up, 382 incident CD and 798 incident UC cases were ascertained. A higher E-DII score was not associated with risk of CD (HR Q4 VS. Q1 = 1.28, 95% CI: 0.94-1.74; P-trend = 0.09) or UC (HR Q4 VS. Q1 = 1.10, 95% CI: 0.90-1.36; P-trend = 0.17). There was an interaction between the E-DII and the polygenic risk score (PRS) for CD on incident CD (P-interaction = 0.023), with an association only among participants with a high PRS (HR Q4 VS. Q1 = 1.64, 95% CI: 1.03-2.61) (P-interaction = 0.023). As compared with the participants with a low PRS for CD and a low E-DII score, participants with high levels of both scores had a particularly higher risk of CD (HR = 3.12; 95% CI: 1.74-5.60).

The association of dietary inflammatory potential with incident CD appears to be amplified by high genetic susceptibility to CD.

Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome. Understanding these changes in the predisease phase provides a means of predicting IBD in high-risk populations and offers insights into possible mechanisms involved in disease pathogenesis. Finally, we discuss strategies to use this information to design interventions aimed at modulating the microbiome as a means of preventing or delaying the onset of IBD.

Ulcerative colitis (UC) is believed to be triggered by a dysregulated inflammatory response to the intestinal microbiota. Acyloxyacyl hydrolase (AOAH) is a unique host lipase that inactivates Gram-negative bacterial lipopolysaccharides (LPS). After finding that AOAH produced in the intestine decreases stimulatory LPS levels in colon contents, we used the dextran sodium sulfate (DSS) model to test the enzyme's ability to prevent colitis in mice. We found that AOAH played a protective role by decreasing colonic inflammation, tissue injury, and barrier permeability. Increasing or decreasing intestinal LPS abundance exacerbated or alleviated colitis, respectively, suggesting that AOAH prevents colitis by reducing stimulatory intestinal LPS levels. AOAH also mitigated colitis-associated colorectal cancer. This highly conserved enzyme may exert its protective effects by preventing LPS-induced injury to the epithelial cell mitochondria that are important for restoring the mucosal epithelial barrier after injury. By decreasing intestinal levels of stimulatory LPS, AOAH prevents colitis and colorectal cancer.

Inflammatory bowel disease (IBD) predisposes individuals to frailty, linked with adverse outcomes. While the Fried Frailty Index (FFI) is a well-established phenotypic tool to assess frailty, its administration is cumbersome. The FRAIL scale, simpler but not widely used in patients with IBD, presents an alternative. We aimed to assess the prevalence of frailty and compare the FRAIL scale with the FFI.

A cohort of patients with IBD underwent assessment using both the FFI and the FRAIL scale. Patients were categorized as non-frail, pre-frail, or frail. The primary outcome was frailty prevalence, while secondary outcomes included comparison of FFI and FRAIL scale and associations between frailty and disease-related factors. Statistical analyses included chi-square tests, ANOVA, Kruskal-Wallis tests, and ROC curve analysis using SPSS v27, with p < 0.05 indicating significance.

Among participants (53.5% female, median age 44), 37% were non-frail, 50% pre-frail, and 13% frail. The FRAIL scale exhibited strong correlation with the FFI for all three categories. Age showed no significant association with frailty. Frail individuals displayed higher inflammatory markers and more severe clinical disease, with frailty more prevalent in patients with UC than CD. Frail individuals also exhibited lower hemoglobin, creatinine, and albumin levels.

Frailty and pre-frailty are prevalent in patients with IBD and not necessarily linked with older age. The FRAIL scale demonstrated excellent correlation with the FFI, offering a practical tool for identifying frailty in IBD without physical measurements. Future studies should explore multivariable models incorporating frailty risk factors and interventions to mitigate adverse outcomes in patients with IBD.

One key area of interest in gastroenterology research is the relationship between Helicobacter pylori (H. pylori) and Inflammatory bowel disease (IBD). Several studies have shown varying results regarding the prevalence of H. pylori in IBD patients and its impact on disease progression, severity, and overall outcome.

This is a prospective cohort study conducted at King Fahad University Hospital in Al Khobar, Saudi Arabia from November 2023 to May 2024 to determine the prevalence of H. pylori in IBD patients and its association with severity. The study included 2 arms for comparison which are IBD patients and control group, IBD will be further classified to CD and UC. Prevalence of H. pylori infection and severity of the disease was compared between these groups.

A total of 360 patients were included in the study which were divided equally into IBD group and control group. The IBD was subdivided into CD with 91 cases and UC with 89 cases. H. Pylori was significantly higher in control group (23.3%) compared with UC cases (13.2%) p value: 0.048. H. pylori infection was significantly high in smokers p value = < 0.0001. The presence of autoimmune disease was significantly associated with H. Pylori infection (16.4%) p value: 0.023.

H. pylori infection was significantly higher in the control group in comparison to IBD group. In addition, smoking and autoimmune disease were significantly associated with H. pylori infection. Finally, the overall association between severity of CD, UC and medication use with H. Pylori were insignificant.

The gut microbiome contributes to chronic inflammatory responses in ulcerative colitis (UC), but molecular mechanisms and disease-relevant effectors remain unclear. Here we analyze the pro-inflammatory properties of colonic fluid obtained during colonoscopy from UC and control patients. In patients with UC, we find that the pelletable effector fraction is composed mostly of bacterial extracellular vesicles (BEVs) that exhibit high IgA-levels and incite strong pro-inflammatory responses in IgA receptor-positive (CD89+) immune cells. Biopsy analyses reveal higher infiltration of CD89+ immune cells in the colonic mucosa from patients with UC than control individuals. Further studies show that IgA-coated BEVs, but not host-derived vesicles nor soluble IgA, are potent activators of pro-inflammatory responses in CD89+ cells. IgA-coated BEVs also exacerbate intestinal inflammation in a dextran sodium sulfate colitis model using transgenic mice expressing human CD89. Our data thus implicate a link between IgA-coated BEVs and intestinal inflammation via CD89+ immune cells, and also hint a potential new therapeutic target for UC.

Ulcerative colitis (UC) is a nonspecific chronic inflammatory disease that occurs in the gastrointestinal tract and is characterized by the breakdown of mucosal immunity. T helper (Th) cells paradigm disequilibrium is a critical for pathogenesis. Maslinic acid (MA), a naturally occurring pentacyclic triterpene isolated from olive pomace and Fructus crataegi, has a variety of applications in both medicine and food. This study investigated the molecular mechanism of the anti-inflammatory potential of MA in a colitis model and activated Th cells. A dextran sulfate sodium-induced experimental colitis model was established. Clinical symptoms were evaluated, and biological samples were collected to examine intestinal mucosal function, inflammation levels, and Th cell-mediated immune responses. The mechanism of the activation-induced cell death (AICD) effect regulated by MA was investigated in the anti-CD3ε/CD28-stimulated Th cell activation model using molecular biotechnology and transcriptome analysis. Key results:MA treatment protected intestinal mucosa, which manifested as reduced inflammatory cytokines, Th cell infiltration, and subset differentiation. Additionally, it was found to suppress Th cell proliferation and differentiation of subsets, regulate cell cycle distribution, and promote AICD by regulating the mitochondria-mediated intrinsic pathway in vitro. JAK-STAT and FcεRI pathways were probable essential pathways, and MAF might be a crucial potential targeting molecule in activated Th cells with MA treatment. This finding demonstrated that MA induced remission of the colitis-related inflammation, which may depend on the resolution of acute inflammation by reducing Th cell-mediated inflammation via AICD induction, emphasizing its promising potential in the treatment of UC.

Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD pathogenesis and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.

Objectives: To explore the possible relationship between Toll-like receptor (TLR) gene encoding and a predictive outcome for the loss of response (LOR) to IFX treatment among Japanese patients with Crohn's disease (CD). Methods: An association analysis that involved 25 single-nucleotide polymorphisms (SNPs) across the TLR1, TLR2, TLR4, TLR6, TLR9, and TLR10 genes was performed on a cohort of 127 Japanese patients with CD. The therapeutic responses were evaluated at 10 weeks, 1 year, and 2 years using three different inheritance models. Results: The CD patients with a G/G genotype of rs5743565 in TLR1 were significantly less likely in the responders at 10 weeks compared with the non-responders (p = 0.023, OR = 0.206). The frequencies of the C/T or T/T genotypes of rs5743604 in the TLR1, G/A, or A/A genotypes of rs13105517 in TLR2, both in the minor allele dominant model, were significantly higher in the responders at 10 weeks as compared with those in the non-responders (p = 0.035, OR = 4.401; p = 0.017, OR = 5.473). The patients with an A/A genotype of rs13105517 in TLR2 in the minor allele recessive model were significantly less likely in the responders at one year of IFX treatment compared with those in the non-responders (p = 0.004, OR = 0.195). Conclusions: The polymorphisms of TLR1 and TLR2 can be useful as biomarkers for predicting initial and secondary LOR to IFX in Japanese CD patients. The IFX response in genetic testing may target molecules for new drugs to overcome the non-response and LOR to IFX.

Background/Objectives: Inflammatory bowel disease (IBD) is characterized by a relapsing-remitting disease course, influenced by dietary factors. This study aims to examine diet quality in IBD patients and investigate its association with disease activity. Methods: In total, 477 participants from a prospective IBD cohort study at two Dutch hospitals were approached to complete a population-specific food frequency questionnaire (GINQ-FFQ) at baseline and after one year. Disease characteristics were assessed at multiple time points. Food-related Quality of Life (FrQoL) was assessed at baseline. Diet quality was measured via the Dietary Inflammatory Index (DII), Mediterranean Diet Score (MDS), Healthy Diet Indicator score (HDI), ultra-processed food intake, and Principal Component Analysis (PCA) to identify dietary patterns. The outcomes were compared to the general Dutch population. Results: In total, 191 participants completed the GINQ-FFQ at baseline, of whom 53 had active disease. Patients in remission had higher FrQoL than patients with active disease (p = 0.020). Diet quality and adherence to specific dietary patterns were not associated with disease activity. However, logistic regression showed a trend toward increased odds of increase in disease activity with an animal protein-rich pattern (OR: 1.479, p = 0.088) and a potential association between the Convenience diet and decreased disease activity (OR: 1.396, p = 0.060). Both the Dutch population and the patient cohort scored poor on all diet quality scores. Conclusions: The current study shows no conclusive evidence of an association between disease activity and both diet quality and dietary patterns in patients with IBD. However, the findings do suggest a possible association between animal protein-rich diets with more disease activity and Convenience-like diets with less disease activity. Furthermore, a similar diet quality was observed in IBD patients and the general Dutch population. Nevertheless, diet quality was generally poor and can be improved.

Despite advances in clinical proteomics, translating protein biomarker discoveries into clinical use remains challenging due to the technical complexity of the validation process. Targeted MS-based proteomics approaches such as parallel reaction monitoring (PRM) offer sensitive and specific assays for biomarker translation. In this study, we developed a multiplex PRM assay using the Stellar mass spectrometry platform to quantify 57 plasma proteins, including 21 FDA-approved proteins. Loading curves (11-points) were performed at 4 sample throughputs (100, 144, 180, and 300 samples per day) using independent, optimized, and scheduled PRM methods. Following optimization, an inflammatory bowel disease (IBD) cohort of plasma samples (493 IBD, 509 matched controls) was analyzed at a throughput of 180 SPD. To monitor system performance, the study also included 1,000 additional injections for system suitability tests, low-, middle-, and high-quality controls, washes, and blanks. Using this approach, we observed high quantifiability (linearity, sensitivity, reproducibility) in the PRM assay and consistent in data acquisition across a large cohort. We also validated the candidate IBD markers, C-reactive protein and orosomucoid protein, identified in a recent discovery experiment.

Ulcerative colitis (UC) is a refractory inflammatory disease that affects the rectum and colon, with pivotal involvement of the rectal environment in relapse initiation. This study was conducted in two phases to examine the differences in gene expression between the rectum and colon and to identify relapse factors.

In ***Study 1, RNA sequencing was performed on biopsies from the colon and rectum of patients with active UC, those with remission UC, and controls. In Study 2, the mucosal impedance (MI) values reflecting mucosal barrier function and the mRNA expression of tight junction proteins and inflammatory cytokines were examined in 32 patients with remission UC and 22 controls. Relapse was monitored prospectively.

In Study 1, comprehensive genetic analysis using RNA sequencing revealed distinct gene profiles in the rectum and sigmoid colon of patients with remission UC. The rectum of these patients exhibited an enriched immune response and apical junction phenotype with persistent upregulation of CLDN2 gene expression. In Study 2, even in patients with remission UC, the MI values in the rectum, but not in the sigmoid colon, were significantly decreased, whereas they were negatively correlated with CLDN2, IL-1β, and IL-6 expressions.

The status of the rectum in patients with remission UC differs from that of the colon, with microinflammation and impaired mucosal barrier function, which are associated with the upregulation of CLDN2, playing a role in relapse.

To analyze the current status of frailty and the primary factors influencing frailty in patients with inflammatory bowel disease (IBD).

We conducted a study using a fixed-point consecutive sampling method to investigate hospitalized patients with IBD aged 18 years or older in the Gastroenterology Department of a general hospital in Anhui, China, from July 2022 to July 2023. We also assessed the prevalence of frailty and malnutrition using the frailty phenotype scale (trial of fatigue, grip strength, physical activity, walking speed, and weight loss) and the Global Leadership Initiative on Malnutrition criteria to analyze the factors influencing frailty.

A total of 300 patients with IBD were included. Of them, 21.67% were classified as frail, 46.67% were prefrail, 31.6% were nonfrail, 35% showed nutritional risk, and 33% were malnourished. The results of bivariate correlation analysis showed that frailty scores were correlated with age, white blood cell count, faecal calprotectin, and C-reactive protein levels and were negatively correlated with body mass index (BMI), hemoglobin, albumin (ALB), and pre-albumin (PALB) levels (r = -0.35, -0.45, -0.55, -0.44, P <.01). The results of multiple linear regression analysis showed that BMI scores, nutritional status, disease state, and ALB levels were important factors influencing frailty (P <.05).

The patients with IBD were frail and prefrail, with a high prevalence of malnutrition. Lower BMI scores, a poor nutritional status, a worse disease state, and lower ALB levels were risk factors for frailty. A cyclical relationship was identified between frailty and malnutrition, with each condition exacerbating the other.

This study aims to develop a nanocarrier system for the oral delivery of β-Carotene (BC) (as a model therapeutic agent) and to test its efficacy in ameliorating inflammation in an ulcerative colitis (UC) patient-derived organoid.

BC was encapsulated in a zein protein nano-cage surface-functionalized with pectin and polyethyleneglycol (PEG). The nanoencapsulated BC (nBC) was characterized for physicochemical properties (size, charge, surface chemistry) and functional properties (radical scavenging, mucoadhesion and penetration, release in simulated digestive fluids). Further, we evaluated the performance of nBC in ameliorating inflammation in Caco-2 and UC patient-derived organoid models.

nBC achieved 75% encapsulation efficiency with improved stability and functional properties when compared to free BC. The nanocarrier was non-cytotoxic and improved mucoadhesion, mucopenetration, and the anti-inflammatory potential of BC. In UC organoids, nBC suppressed dextran sulfate sodium (DSS)-induced TNF-α and IL-8 production by approximately 70% and 31%, respectively, which was significantly higher than free BC at comparable concentrations.

The protein-polymer nanoencapsulation strategy showed promise in protecting BC and overcoming intestinal mucus barriers for an improved anti-inflammatory effect in the organoid model. Further studies using animal models are warranted for establishing pharmacokinetics, tissue distribution, and therapeutic index of orally delivered nBC.

This article provides an overview of the advancements in the application of fecal microbiota transplantation (FMT) in treating diseases related to intestinal dysbiosis. FMT involves the transfer of healthy donor fecal microbiota into the patient's body, aiming to restore the balance of intestinal microbiota and thereby treat a variety of intestinal diseases such as recurrent Clostridioides difficile infection (rCDI), inflammatory bowel disease (IBD), constipation, short bowel syndrome (SBS), and irritable bowel syndrome (IBS). While FMT has shown high efficacy in the treatment of rCDI, further research is needed for its application in other chronic conditions. This article elaborates on the application of FMT in intestinal diseases and the mechanisms of intestinal dysbiosis, as well as discusses key factors influencing the effectiveness of FMT, including donor selection, recipient characteristics, treatment protocols, and methods for assessing microbiota. Additionally, it emphasizes the key to successful FMT. Future research should focus on optimizing the FMT process to ensure long-term safety and explore the potential application of FMT in a broader range of medical conditions.

Although increasingly appreciated, little is known about the prevalence of fecal urgency, fecal incontinence and differences between patients' and physicians' perception in inflammatory bowel disease (IBD).

We performed an online patient and physician survey to evaluate the assessment, prevalence and impact of fecal urgency and incontinence in IBD.

A total of 593 patients (44.0% ulcerative colitis (UC), 53.5% Crohn's disease (CD), 2.2% indeterminate colitis, 2 not specified) completed the survey (65.8% females, mean age 47.1 years). Fecal urgency was often reported (UC: 98.5%, CD: 96.2%) and was prevalent even during remission (UC: 65.9%, CD: 68.5%). Fecal urgency considerably impacted daily activities (visual analog scale [VAS] 5, IQR 3-8). Yet, 22.8% of patients have never discussed fecal urgency with their physicians. Fecal incontinence was experienced by 44.7% of patients and 7.9% on a weekly basis. Diapers/pads were required at least once a month in 20.4% of patients. However, 29.7% of patients never talked with their physician about fecal incontinence. UC was an independent predictor for the presence of moderate-severe fecal urgency (OR 1.65, 95% CI 1.13-2.41) and fecal incontinence (OR 1.77, 95% CI 1.22-2.59). All physicians claimed to regularly inquire about fecal urgency and incontinence. However, the impact of these symptoms on daily activities was overestimated compared with the patient feedback (median VAS 8 vs. 5, p = 0.0113, and 9 vs. 5, p = 0.0187).

Fecal urgency and incontinence are burdensome symptoms in IBD, with a similar prevalence in UC and CD. A mismatch was found between the physician and patient perception. These symptoms should be addressed during outpatient visits.

Diet is an important environmental factor in inflammatory bowel disease (IBD) onset and disease course, but analyses are hindered by its complexity. We aim to explore the Sparse Grouped Least Absolute Shrinkage and Selection Operator (Sparse Grouped LASSO or SGL) method to study whether different food categorizations, representing different dietary patterns, can predict flares in IBD.

Baseline data on habitual dietary intake and longitudinal data on disease course were collected over a 24 month-period in two distinct cohorts. Food items were classified into 22 food groups. These were further classified into three diet categorizations: 1. Plant vs animal vs mixed; 2. Potentially healthy vs potentially unhealthy vs neutral; 3. Ultra-processed vs not ultra-processed. The SGL parameter 'lambda' identifies important groups using a-priori group information, while allowing for only a subset of variables within a group to be important predictors.

Of 724 eligible patients, 427 were in remission at baseline and were included in the SGL analyses. 106 (24.8 %) included patients developed a flare within 11.2 ± 6.6 months (65.1 % female, 34 % ulcerative colitis, mean age 43.3 ± 14.7 years). They had a higher crude food intake of red meat (p = 0.028) and vegetables (p = 0.027) than those who stayed in remission. Prediction models for flare development were moderate with AUC varying between 0.425 and 0.542 for model 1, 0.512 and 0.562 for model 2 and 0.451 and 0.612 for model 3. All models showed red meat, legumes and vegetables as the first selected predicting variables. However, female sex and energy intake had the highest predictive values in all 3 models.

Categorization of the same food groups in different ways influences the predictive value of the SGL method. The current exploration of the SGL method shows that food might not be the most important predictor of flares in IBD.

Background: A significant concern for patients with Inflammatory Bowel Disease (IBD) is predicting and managing disease flares. While healthcare providers rely on biomarkers, providing conclusive patient advice remains challenging. This review explores the role of lifestyle, psychological health, and environmental exposures in the prediction and management of IBD flares. Methods: This review followed PRISMA guidelines (2020). A structured search was conducted in PubMed for articles published between 2012 and 2024, using free and Medical Subject Heading (MeSH) terms for predicting factors in IBD. Inclusion criteria included studies reporting primary data on modifiable clinical or environmental predictors of IBD relapse, excluding studies on post-operative investigations, treatment cessation, and pediatric or pregnant populations. The Mixed Method Appraisal Tool (MMAT) was used to assess the quality of the studies. Results: Out of 2287 identified citations, 58 articles were included. Several modifiable factors influencing disease flares were identified, including psychological stress, sleep disturbances, smoking, and nutrition. Poor sleep quality and mental health were linked to increased flare risks, while smoking was associated with higher relapse rates in Crohn's disease. Environmental exposures, such as heat waves and high-altitude regions, also contributed. Predictive models integrating clinical, lifestyle, and psychological factors showed promising accuracy but require further refinement. Limitations of this review include the potential for publication bias, variability in flare definitions, and limited sample sizes Conclusions: Key predictors of IBD flares include dietary factors, psychological stress, poor sleep quality, and pharmacological influences. Personalized approaches integrating these predictors can optimize disease control and improve patient outcomes.

Immunity is a fundamental aspect of animal biology, defined as the host's ability to detect and defend against harmful pathogens and toxic substances to preserve homeostasis. However, immune defenses are metabolically demanding, requiring the efficient allocation of limited resources to balance immune function with other physiological and developmental needs. To achieve this balance, organisms have evolved sophisticated signaling networks that enable precise, context-specific responses to internal and external cues. These networks are essential for survival and adaptation in multicellular systems. Central to this regulatory architecture is the STAT (signal transducer and activator of Transcription) family, a group of versatile signaling molecules that govern a wide array of biological processes across eukaryotes. STAT signaling demonstrates remarkable plasticity, from orchestrating host defense mechanisms to regulating dietary metabolism. Despite its critical role, the cell-specific and context-dependent nuances of STAT signaling remain incompletely understood, highlighting a significant gap in our understanding. This review delves into emerging perspectives on immunity, presenting dynamic frameworks to explore the complexity and adaptability of STAT signaling and the underlying logic driving cellular decision-making. It emphasizes how STAT pathways integrate diverse physiological processes, from immune responses to dietary regulation, ultimately supporting organismal balance and homeostasis.

Background: The global burden of inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, is constantly rising. As IBDs significantly reduce patients' quality of life, prevention and efficient treatment of IBDs are of paramount importance. Although the molecular mechanisms underlying IBD pathogenesis are still not completely understood, numerous studies indicate the essential role of oxidative stress in the progression of the diseases. Objective: The aim of this study was to investigate whether prophylactic administration of recombinant banana lectin (rBanLec) could positively affect antioxidative mechanisms in the colon and thus prevent or alleviate the severity of experimental colitis induced in C57BL/6 mice. Methods: The prophylactic potential of rBanLec, a mannose-binding lectin with immunomodulatory properties, was investigated in a model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6 mice. Mice received rBanLec at various doses (0.1, 1 and 10 μg/mL) before the induction of colitis. The severity of the disease was assessed by weight loss and reduction in colon length, and correlated with histopathological findings, cytokine milieu, and oxidative stress markers in the colon. Results: The obtained results revealed that pretreatment with a low dose of rBanLec (0.1 μg/mL) significantly reduced the severity of TNBS-induced colitis, as indicated by reduced weight loss, less severe histopathological damage, and a favorable anti-inflammatory cytokine milieu (increased IL-10 and TGFβ). In addition, rBanLec pretreatment improved the activity of antioxidant enzymes (SOD, CAT, and GST) and reduced markers of oxidative stress such as nitric oxide levels at the peak of the disease. In contrast, higher doses of rBanLec exacerbated inflammatory responses. Conclusions: Our findings indicate that at low doses rBanLec can alleviate the severity of colitis by modulating oxidative stress and promoting anti-inflammatory cytokine responses, positioning rBanLec as a potential candidate for treating IBDs.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD), ulcerative colitis (UC), and IBD unclassified (IBD-U), is a complex intestinal disorder influenced by genetic, environmental, and microbial factors. Recent evidence highlights the gut microbiota as a pivotal biomarker and modulator in IBD pathogenesis. Dysbiosis, characterized by reduced microbial diversity and altered composition, is a hallmark of IBD. A consistent decrease in anti-inflammatory bacteria, such as Faecalibacterium prausnitzii, and an increase in pro-inflammatory species, including Escherichia coli, have been observed. Metabolomic studies reveal decreased short-chain fatty acids (SCFAs) and secondary bile acids, critical for gut homeostasis, alongside elevated pro-inflammatory metabolites. The gut microbiota interacts with host immune pathways, influencing morphogens, glycosylation, and podoplanin (PDPN) expression. The disruption of glycosylation impairs mucosal barriers, while aberrant PDPN activity exacerbates inflammation. Additionally, microbial alterations contribute to oxidative stress, further destabilizing intestinal barriers. These molecular and cellular disruptions underscore the role of the microbiome in IBD pathophysiology. Emerging therapeutic strategies, including probiotics, prebiotics, and dietary interventions, aim to restore microbial balance and mitigate inflammation. Advanced studies on microbiota-targeted therapies reveal their potential to reduce disease severity and improve patient outcomes. Nevertheless, further research is needed to elucidate the bidirectional interactions between the gut microbiome and host immune responses and to translate these insights into clinical applications. This review consolidates current findings on the gut microbiota's role in IBD, emphasizing its diagnostic and therapeutic implications, and advocates for the continued exploration of microbiome-based interventions to combat this debilitating disease.

Over a century ago, Virchow proposed that cancer represents a chronically inflamed, poorly healing wound. Normal wound healing is represented by a transitory phase of inflammation, followed by a pro-resolution phase, with prostaglandin (PGE2/PGD2)-induced 'lipid class switching' producing inflammation-quenching lipoxins (LXA4, LXB4).

We explored if lipid dysregulation in colorectal cancers (CRCs) is driven by a failure to resolve inflammation.

We performed liquid chromatography and tandem mass spectrometry (LC-MS/MS) untargeted analysis of 40 human CRC and normal paired samples and targeted, quantitative analysis of 81 human CRC and normal paired samples. We integrated analysis of lipidomics, quantitative reverse transcription-PCR, large scale gene expression, and spatial transcriptomics with public scRNASEQ data to characterize pattern, expression and cellular localisation of genes that produce and modify lipid mediators.

Targeted, quantitative LC-MS/MS demonstrated a marked imbalance of pro-inflammatory mediators, with a dearth of resolving lipid mediators. In tumours, we observed prominent over-expression of arachidonic acid derivatives, the genes encoding their synthetic enzymes and receptors, but poor expression of genes producing pro-resolving synthetic enzymes and resultant lipoxins (LXA4, LXB4) and associated receptors. These results indicate that CRC is the product of defective lipid class switching likely related to inadequate or ineffective levels of PGE2/PGD2.

We show that the lipidomic profile of CRC tumours exhibits a distinct pro-inflammatory bias with a deficiency of endogenous resolving mediators secondary to defective lipid class switching. These observations pave the way for 'resolution medicine', a novel therapeutic approach for inducing or providing resolvins to mitigate the chronic inflammation driving cancer growth and progression.

Several therapies have been approved to treat Crohn's disease (CD) and ulcerative colitis (UC), indicating that both diseases may share the same molecular subtypes. The aim of this study is to identify shared patient subtypes with common molecular drivers of disease.

Five public datasets with 406 CD and 421 UC samples were integrated to identify molecular subtypes. Then, the patient labels from 6 independent datasets and 8 treatment datasets were predicted for validating subtypes and identifying the relationship with response status of corticosteroids, infliximab, vedolizumab, and ustekinumab.

Two molecular subtypes were identified from the training datasets, in which CD and UC patients were relatively evenly represented in each subtype. We found 6 S1-specific gene modules related to innate/adaptive immune responses and tissue remodeling and 9 S1-specific cell types (cycling T cells, Tregs, CD8+ lamina propria, follicular B cells, cycling B cells, plasma cells, inflammatory monocytes, inflammatory fibroblasts, and postcapillary venules). Subtype S2 was associated with 3 modules related to metabolism functions and 4 cell types (immature enterocytes, transit amplifying cells, immature goblet cells, and WNT5B+ cells). The subtypes can be replicated in 6 independent datasets based on a 20-gene classifier. Furthermore, response rates to 4 treatments in subtype S2 were significantly higher than those in subtype S1.

This study discovered and validated a robust transcriptome-based molecular classification shared by CD and UC and built a 20-gene classifier. Because 2 subtypes have different molecular mechanisms and drug response, our classification may aid interpretation of heterogeneous molecular and clinical information in inflammatory bowel disease patients.

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory disorder that affects not only the gastrointestinal tract but also extraintestinal organs, leading to various extraintestinal manifestations and complications. Among these, musculoskeletal disorders such as osteoporosis, sarcopenia, and axial and peripheral spondyloarthritis are the most commonly observed. These conditions arise from complex mechanisms, including chronic inflammation, malnutrition, gut dysbiosis, and glucocorticoid use, all of which contribute to reduced bone density, muscle loss, and joint inflammation. Osteoporosis and sarcopenia may co-occur as osteosarcopenia, a condition that heightens the risk of fractures, impairs physical performance, and diminishes quality of life, particularly in elderly patients with IBD. Holistic management strategies, including lifestyle modifications, calcium, and vitamin D supplementation, resistance training, and pharmacological interventions, are essential for mitigating the impact of these conditions. Spondyloarthritis, which affects both axial and peripheral joints, further complicates disease management and significantly compromises joint health. Timely diagnosis and appropriate medical interventions, such as administration of nonsteroidal anti-inflammatory drugs and biologics, are critical for preventing chronic joint damage and disability. Moreover, a multidisciplinary approach that addresses both metabolic and inflammatory aspects is essential for optimizing physical function and improving treatment outcomes in patients who have IBD with musculoskeletal involvement.

Disease activity scores are efficacy endpoints in clinical trials of inflammatory bowel disease (IBD) therapies. Crohn's disease activity index (CDAI), Mayo endoscopic score (MES) and Mayo score are frequently used in clinical trials. They rely on either the physician's observation of the inflammatory state of the patient's gastrointestinal tissue alone or combined with the patient's subjective evaluation of general wellbeing. Given the importance of these scores in evaluating the efficacy of drug treatment and disease severity, there has been interest in developing a computational approach to reliably predict these scores. A promising approach is using mechanistic models such as quantitative systems pharmacology (QSP) which simulate the mechanisms of the disease and its modulation by the drug pharmacology. However, extending QSP model simulations to clinical score predictions has been challenging due to the limited availability of gut biopsy measurements and the subjective nature of some of the evaluation criteria for these scores that cannot be described using mechanistic relationships. In this perspective, we examine details of IBD disease activity scores and current progress in building predictive models for these scores (such as biomarkers for disease activity). Then, we propose a method to leverage simulated markers of inflammation from a QSP model to predict IBD clinical scores using a machine learning algorithm. We will demonstrate how this combined approach can be used to (1) explore mechanistic insights underlying clinical observations; and (2) simulate novel therapeutic strategies that could potentially improve clinical outcomes.

To achieve effective long-term synergistic treatment of inflammatory bowel disease (IBD) with probiotics, we developed a versatile inulin/trans-ferulic acid/silk sericin nanoparticles-nourished probiotic complex. Inulin/TFA/SS nanoparticles were fabricated by inulin, trans-ferulic acid (TFA), and silk sericin (SS), and then loaded onto the surface of poly-l-lysine (PLL) and poly-glutamic acid (PGA)-coated Bifidobacterium longum (BL) to obtain BL@PLL-PGA-Inulin/TFA/SS NPs (BL@PP-NPs). This design simultaneously endowed the complex with excellent gastrointestinal resistance, antioxidant, and anti-inflammation abilities. Moreover, the inulin in the nanoparticles acts as a prebiotic, promoting the Bifidobacterium's rapid proliferation to exert effects within a short period. Compared with uncoated BL, BL@PP-NPs exhibited excellent gastric acid tolerance and up to 31.32-fold colonic colonization, and the ROS scavenging and proliferative capacity were increased by 5.61- and 1.39-fold, respectively. In a mouse model of dextran sulfate sodium (DSS)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis, the components of Inulin/TFA/SS NPs synergized with probiotics to efficiently treat IBD by attenuating oxidative stress, decreasing inflammation, repairing intestinal barrier, and promoting the rapid proliferation of probiotics to reverse gut microbial disorders. Collectively, food-grade BL@PP-NPs represent a novel approach to probiotic modification that offers an effective, safe, and synergistic therapy for IBD.

Existing gastrointestinal (GI) diagnostic tools are unable to non-invasively monitor mucosal tight junction integrity in vivo beyond the esophagus. In the GI tract, local inflammatory processes induce alterations in tight junction proteins, enhancing paracellular ion permeability. Although transepithelial electrical resistance (TEER) may be used in the laboratory to assess mucosal barrier integrity, there are no existing methodologies for characterizing tight junction dilation in vivo. Addressing this technology gap, intraluminal bioimpedance sensing may be employed as a localized, non-invasive surrogate to TEER electrodes used in cell cultures. Thus far, bioimpedance has only been implemented in esophagogastroduodenoscopy (EGD) due to the need for external electronics connections. In this work, we develop a novel, noise-resilient Bluetooth-enabled ingestible device for the continuous, non-invasive measurement of intestinal mucosal "leakiness." As a proof-of-concept, we validate wireless impedance readout on excised porcine tissues in motion. Through an animal study, we demonstrate how the device exhibits altered impedance response to tight junction dilation induced on mice colonic tissue through calcium-chelator exposure. Device measurements are validated using standard benchtop methods for assessing mucosal permeability.

Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD.

Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation.

The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn's disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19).

Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis.

Background/Objectives: This study aimed to compare the association of ustekinumab (UST) drug clearance (CL) and trough drug concentrations with disease activity in patients with inflammatory bowel diseases (IBDs). Methods: A prospective cohort of 83 patients with IBD receiving maintenance therapy with 90 mg subcutaneous UST was analyzed using Bayesian PK modeling. UST concentrations and antibodies to UST (ATU) were collected at the trough and measured using a drug-tolerant homogenous mobility shift assay (HMSA). CL was estimated using Bayesian estimation methods with priors from a previous population pharmacokinetic study specifically reparametrized using HMSA. Outcomes were combined clinical and biochemical remission and endoscopic healing index (EHI) score, a validated marker of endoscopic active disease in IBD. Statistical analysis consisted of linear and nonlinear mixed effect models for repeated time-to-event analysis. Results: A total of 83 patients with IBD were enrolled (median age 42 years, 52% female) and evaluated across 312 dose cycles (median follow-up: 279 days, median of 3 cycles/patient). Median concentrations and CL were 5.0 µg/mL and 0.157 L/day, respectively. Most patients (89%) were exposed to other biologics before starting UST, which was associated with lower rates of clinical and biochemical remission (p = 0.01). Longitudinal changes in concentrations were not associated with remission (p = 0.53). Conversely, higher CL was associated with a lower likelihood of remission (p < 0.01). EHI > 50 points (endoscopic active disease, n = 303 cycles) was associated with higher UST CL (p < 0.01). Conclusions: UST CL was more strongly associated with clinical and biochemical outcomes than trough concentrations, highlighting its potential role in therapy optimization.