Search Results (4,339)

Ulcerative colitis (UC) is a chronic progressive inflammatory bowel disease, with evolutive potential for extension to the entire colon, development of complications and need for colectomy. Therapeutic goals in UC have moved from symptom control to more stringent outcomes such as endoscopic and histologic remission, which have been observed to correlate with improved long-term outcomes. Disease clearance, a composite endpoint simultaneously including clinical remission, endoscopic and histologic healing, has been recently proposed as the ultimate target. A treat-to-target approach, as endorsed by the STRIDE II consensus, with a tight monitoring and treatment escalation when predefined endpoints are not reached, is proposed as a strategy to achieve complete disease control. However, unlike Crohn’s disease (CD), the evidence supporting this approach for the management of UC is limited and its implementation in routine clinical practice is not widely diffused. Recent real-life data show that almost half of UC patients are not adequately controlled with current therapies according to STRIDE II criteria, due to steroid overuse, persistent signs of inflammation, active extra-intestinal manifestations and impaired quality of life. This perspective paper explores current evidence and future directions on treat-to-target strategies in UC for clinical research and practice. Full article

Early life is a critical window for immune system development, during which the gut microbiome shapes innate immunity, antigen presentation, and adaptive immune maturation. Disruptions in microbial colonization—driven by factors such as cesarean delivery, antibiotic exposure, and formula feeding—deplete beneficial early-life taxa (e.g., Bifidobacterium, Bacteroides, and Enterococcus) and impair key microbial functions, including short-chain fatty acid (SCFA) production by these keystone species, alongside regulatory T cell induction. These dysbiosis patterns are associated with an increased risk of pediatric autoimmune diseases, notably type 1 diabetes, inflammatory bowel disease, celiac disease, and juvenile idiopathic arthritis. This review synthesizes current evidence on how the early-life microbiota influences immune maturation, with potential effects on the development of autoimmune diseases later in life. We specifically focus on human observational and intervention studies, where treatments with probiotics, synbiotics, vaginal microbial transfer, or maternal fecal microbiota transplantations have been shown to partially restore a disrupted microbiome. While restoration of the gut microbiome composition and function is the main reported outcome of these studies, to date, no reports have disclosed direct prevention of autoimmune disease development by targeting the early-life gut microbiome. In this regard, a better understanding of the early-life microbiome–immune axis is essential for developing targeted preventive strategies. Future research must prioritize longitudinal evaluation of autoimmune outcomes after microbiome modulation to reduce the burden of chronic immune-mediated diseases. Full article

Ulcerative colitis (UC) is an inflammatory bowel disease associated with oxidative stress. Pogostemon oil (PO) exhibits potent antioxidant and anti-inflammatory activities but is limited by high volatility and poor gastrointestinal stability. In this study, sporopollenin exine capsules (SECs) were engineered as natural micro-carriers for PO, achieving efficient encapsulation (η > 69%) and a high adsorption capacity (27.64 g/g). A pH-sensitive calcium alginate shell was subsequently applied to construct colon-targeted microspheres (Ca-Alg@PO-SECs). The resulting system improved the thermal and photostability of PO. In vitro dissolution assays confirmed the system’s pH-responsiveness, maintaining integrity under simulated gastric conditions while enabling localized release at intestinal pH. In a DSS-induced acute UC mouse model, Ca-Alg@PO-SECs effectively alleviated clinical symptoms, as evidenced by improved body weight, colon length, and disease activity index. At the inflammatory level, the formulation modulated key cytokines (IL-1β, IL-6, and IL-10). Overall, Ca-Alg@PO-SECs provides a biocompatible, colon-targeted delivery strategy that preserves the bioactivity of essential oils and offers a promising preclinical approach for localized UC therapy. Full article

Colitis-associated colorectal cancer (CAC) represents a distinct subtype of colorectal malignancy that arises in the setting of chronic inflammatory bowel disease (IBD). Unlike sporadic colorectal cancer, CAC develops through inflammation-driven molecular pathways, in which epigenetic alterations play a pivotal role in tumor initiation and progression. This review highlights the major epigenetic mechanisms implicated in CAC, including DNA methylation, histone modifications, and microRNA (miRNA) dysregulation. Aberrant DNA methylation patterns, such as promoter hypermethylation of tumor suppressor genes and global hypomethylation, contribute to genomic instability and altered gene expression. In parallel, inflammation-induced changes in histone configuration modulate chromatin accessibility and transcriptional activity of key oncogenic and tumor-suppressive pathways. Furthermore, deregulated miRNAs influence multiple aspects of CAC pathogenesis by targeting genes involved in inflammation and tumor progression. Understanding these epigenetic processes provides valuable insights into the development of colorectal malignancy and identifies potential biomarkers for early detection and intervention in colitis-associated colorectal cancer. Full article

Inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are chronic inflammatory diseases that share immune dysregulation and mitochondrial dysfunction. Understanding the molecular mechanisms linking these diseases to mitochondrial dysfunction is crucial for developing novel diagnostic and therapeutic strategies. Datasets related to IBD and RA were obtained from the Gene Expression Omnibus database. Differentially expressed mitochondrial dysfunction-related genes (MDRGs) were identified using differential expression analysis. Weighted gene co-expression network analysis was performed to identify crosstalk genes (CGs). Logistic regression and support vector machine (SVM) models were constructed using least absolute shrinkage and selection operator regression to identify hub genes. Additionally, the differential expression and diagnostic value of the hub genes were verified using quantitative reverse transcriptase–polymerase chain reaction and validation sets. Finally, immune infiltration analysis was conducted to assess the role of immune cells in IBD and RA. A total of 87 CGs associated with mitochondrial dysfunction were identified between IBD and RA, among which PDIA4 and DUSP6 were identified as hub genes. Twenty proteins, including ERO1A, MAPK7, and P4HB, were identified as key proteins that interacted with PDIA4 and DUSP6. The area under the curve (AUC) of the ROC curves for IBD and RA based on the DUSP6 and PDIA4 diagnostic models were 0.664 and 0.856, respectively. The qRT-PCR results indicated that PDIA4 and DUSP6 were overexpressed in IBD and RA. Seven immune cell types, including activated B cells, activated dendritic cells, and eosinophils showed significant differences in the IBD and RA groups. Our findings highlight the close association between IBD, RA, and mitochondrial dysfunction. PDIA4 and DUSP6 may serve as potential biomarkers of mitochondrial dysfunction in patients with IBD and RA. Full article

Abdominal pain is the cardinal symptom of irritable bowel syndrome (IBS) and the primary determinant of disease burden and healthcare utilization. Despite its diagnostic centrality and high prevalence across all IBS subtypes, effective management remains a clinical challenge. This narrative review explores the pathophysiological mechanisms underlying IBS-related pain, emphasizing the role of visceral hypersensitivity, altered brain–gut communication, and luminal factors such as gas and distension. We examine current guideline recommendations, real-world treatment patterns, and evidence supporting both pharmacological and non-pharmacological interventions. Particular focus is placed on the fixed-dose combination of alverine citrate/simeticone, which targets both motor and sensory pathways. Mechanistic studies demonstrate its smooth muscle relaxant, antinociceptive, and anti-inflammatory actions. Clinical trials support its efficacy in reducing pain, improving quality of life, and lowering healthcare resource use. Despite these advances, several unmet needs remain, including subtype-specific treatment strategies, mechanistic biomarkers, and broader access to integrated care. The review concludes with a call for more personalized, mechanism-based approaches to pain management in IBS, with alverine citrate/simeticone offering a pragmatic option within this evolving therapeutic framework. Full article

Inflammatory Bowel Diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, immune-mediated disorders marked by persistent and recurrent inflammation of the gastrointestinal tract. Over the past two decades, major advances in understanding the immunologic and molecular pathways that drive intestinal injury have transformed the therapeutic landscape. This progress has enabled the development of novel biologics and small-molecule agents that more precisely target dysregulated immune responses, thereby improving clinical outcomes and quality of life for many patients. Despite these therapeutic advances, IBD remains a highly heterogeneous condition. Patients differ widely in disease phenotype, progression, and response to specific treatments. Consequently, selecting the most effective therapy for an individual patient requires careful consideration of clinical features, molecular markers, and prior treatment history. The shift toward personalized, prediction-based treatment strategies aims to optimize the timing and choice of therapy, minimize unnecessary exposure to ineffective drugs, and ultimately alter the natural course of disease. In this review, we provide a comprehensive overview of current evidence guiding drug positioning in IBD, with particular emphasis on biologic therapies and small-molecule inhibitors. We also examine emerging biomarkers, clinical predictors of response, and real-world factors that influence therapeutic decision-making. Finally, we discuss the challenges and limitations that continue to hinder widespread implementation of personalized strategies, underscoring the need for further research to integrate precision medicine into routine IBD care. Full article

Background: Vedolizumab and ustekinumab are increasingly used off-label in pediatric inflammatory bowel disease (IBD) unresponsive or refractory to anti–TNFα therapy. Despite their increasing use in clinical practice, evidence in the pediatric population remains limited, especially regarding therapeutic exposure thresholds and the clinical utility of therapeutic drug monitoring (TDM). Methods: We report a series of five pediatric cases with Crohn’s disease or ulcerative colitis treated with ustekinumab or vedolizumab after anti-TNFα failure. Trough drug concentrations, anti-drug antibodies (ADAs), clinical scores (PCDAI/PUCAI), biomarkers (fecal calprotectin, C-reactive protein), and endoscopic findings were assessed longitudinally. Results: In all cases, we observed recurrent discordance between clinical indices (PCDAI/PUCAI), biochemical markers, and endoscopic activity. Clinical improvement frequently correlated with trough concentrations above commonly cited adult-derived reference ranges (>15 µg/mL for vedolizumab; >3 µg/mL for ustekinumab), although this alignment was not uniform across patients. Notably, one patient developed high-titre ADAs with undetectable ustekinumab levels, yet remained clinically stable, suggesting substantial interindividual variability in pharmacokinetics, immunogenicity, and disease control. Conclusions: Ustekinumab and vedolizumab are promising off-label options for pediatric refractory IBD. In this case series, TDM contributed to the interpretation of pharmacokinetic variability and immunogenicity, offering contextual insights that may support dose adjustments and therapeutic decision-making. Integrating TDM with clinical, biochemical, and endoscopic monitoring may improve optimize individualized treatment in this complex and vulnerable patient group. Full article

Adherent-invasive E. coli (AIEC) is closely related to inflammatory bowel disease (IBD). However, its pathogenic mechanism has not yet been fully elucidated. Using a BLASTP search, we discovered that the amino acid sequence of a putative protein (UFP37798.1) in the AIEC LF82 strain is highly homologous to some regulators in the SlyA family. We named it EruA. We displayed the secondary structures of EruA using bioinformatics, overexpressed the His₆-tagged EruA protein using SDS-PAGE, and dissected the genetic organization of the eruA chromosomal region using 5′RACE. We constructed an eruA deletion mutant (ΔeruA) and a complementary strain (CΔeruA) of the LF82 strain. The transcriptomes of wild-type (WT) and ΔeruA bacteria were compared using RNA sequencing and qRT-PCR, thereby identifying 32 differentially expressed genes (DEGs). Based on YASARA software and EMSA analysis, EruA directly binds to the consensus sequences (P_fimA and P_tnaB) in the promoter region of the fimA and tnaB genes from these DEGs. By using a super-resolution confocal microscope (SCM), counting CFUs of colonies on plates, indole quantification, and crystal violet staining of biofilms adhered to tubes or 96-well plates, we found that EruA activates the fimA to promote bacterial adhesion to intestinal epithelial cells and activates the tnaB to enhance bacterial indole production and biofilm formation. Moreover, EruA helps AIEC resist environmental stress and enhances bacterial survival within macrophages as well as loading in mouse tissues. Notably, EruA promotes AIEC colonization in the colons of mice and exacerbates intestinal inflammation caused by bacterial infection in mice with DSS-induced inflammatory colitis, manifested by weight loss, colon length shortening, and pathological changes in colon tissues. Therefore, EruA plays a key role in the pathogenicity of AIEC. Full article

Background: Female individuals with inflammatory bowel diseases (IBDs) are more likely to develop restrictive eating disorders (REDs), with both conditions appearing to share common pathophysiological pathways. We conducted a case–control study exploring eating symptomatology and interoceptive profiles in female adolescents with IBDs compared with adolescents diagnosed with REDs, in order to test the hypothesis that the two clinical populations exhibit similar interoceptive characteristics. Methods: We recruited 33 female adolescents with IBDs and 54 controls with REDs matched for age and gender. All participants completed a validated psychometric battery assessing eating disorder features (EDI-3) and interoceptive awareness (MAIA-2). Results: Twenty-seven percent of patients with IBD scored above the cut-off (>70th percentile) on the EDI-3 Eating Disorder Risk Composite (EDRC), showing an eating and interoceptive profile comparable to that of patients with REDs. The two sub-cohorts within the IBD sample differed in the ‘Not-Worrying’ and ‘Trusting’ MAIA-2 subscales, with the IBD cohort at risk of developing an ED reporting lower scores. Conclusions: Our findings indicate comparable interoceptive profiles between adolescents with IBDs who are at risk of developing EDs and patients with a confirmed diagnosis of REDs. This similarity underscores the need to further investigate the shared pathogenic mechanisms underlying these conditions, particularly the role of the gut–brain axis (GBA). Full article

Inflammatory bowel disease (IBD) arises from chronic dysregulation at the epithelial–stromal interface, creating a need for in vitro systems that better capture these interactions. In this study, we developed a 3D co-culture platform in which HT-29 intestinal epithelial cells and IMR-90 fibroblasts are embedded within an alginate–gelatin hydrogel, alongside a complementary interface model using a plasma-treated electrospun mesh to spatially compartmentalize stromal and epithelial layers. We first assessed metabolic activity, viability, and proliferation across several epithelial-to-fibroblast ratios and identified 1:0.5 as the most supportive of epithelial expansion. The A1G7 hydrogel maintained high viability (>92%) and sustained growth in all mono- and co-cultures. To evaluate inflammatory competence, models were stimulated with lipopolysaccharide (LPS), administered either within the hydrogel or through the culture medium. LPS exposure increased TNF-α and IL-1β secretion in both configurations, with the magnitude of the response depending on the delivery route. Treatment with dexamethasone consistently reduced cytokine levels, confirming the model’s suitability for pharmacological testing. Together, these results demonstrate that the alginate–gelatin system provides a reproducible epithelial–stromal platform with quantifiable inflammatory readouts, offering a practical foundation for mechanistic studies and early-stage screening of anti-inflammatory therapeutics in IBD. Full article

Background and Objectives: Telemedicine has become an essential component of chronic Inflammatory Bowel Disease (IBD) care, yet the factors that shape patient satisfaction with remote consultations remain only partially understood. This study aimed to assess satisfaction with institutional telemedicine services among Italian patients with ulcerative colitis (UC) and Crohn’s disease (CD), and to identify sociodemographic, clinical and organisational predictors to inform more person-centred telehealth models. Materials and Methods: We conducted a prospective, multi-centre, cross-sectional study in three IBD units in northern, central and southern Italy between June and October 2024. Consecutive adult patients who had completed a scheduled, non-emergency telemedicine visit were invited within 24–48 h to complete an online questionnaire including the Italian Telemedicine Satisfaction Questionnaire (I-TSQ), sociodemographic items, IBD-related variables, and telemedicine process indicators (accessibility, technology usability, technical support, time saved). Data were analysed descriptively and with multivariable linear regression to determine independent predictors of satisfaction, adjusting for recruiting centre. Results: A total of 705 patients participated (54.9% UC; 55.3% disease duration > 10 years). Overall, telemedicine satisfaction was high (mean I-TSQ total 57.5 ± 4.9; range 35–70), and all respondents reported reduced indirect costs compared with in-person visits. Greater ease of technology use, more frequent contact with the care team, male sex, older age, and employment were independently associated with higher satisfaction scores. Conversely, first-ever teleconsultations, CD, subcutaneous therapies, more difficult platform access, and the need for technical support were linked to lower satisfaction. Model fit was modest (R² up to 0.20), suggesting the presence of additional unmeasured relational and contextual factors. Conclusions: Telemedicine for IBD is widely accepted in Italy, but satisfaction is strongly conditioned by digital usability, previous experience, and clinical complexity. Tailored telehealth pathways that incorporate user-friendly platforms, proactive technical support, and attention to vulnerable subgroups are needed to translate high satisfaction into sustained, equitable remote care. Full article

Background: Liver X receptors (LXRs) are critical regulators of cholesterol homeostasis that modulate T cell function with anti-inflammatory effects. LXR downregulation has been implicated in the pathogenesis of inflammatory bowel disease (IBD), although its underlying mechanisms remain to be fully elucidated. Recent evidence has confirmed the link between T cell senescence and autoimmune diseases. Here, we sought to investigate whether and how LXRs regulate T cell senescence in controlling intestinal inflammation. Methods and Results: We found that LXRβ expression was decreased in the colons of mice with experimental colitis, and LXRβ deficiency (Lxrβ^−/−) significantly aggravated their colitis. Intriguingly, this finding was accompanied by enhanced CD4⁺ T cell senescence both in the colons and spleens of Lxrβ^−/− mice, evidenced by upregulation of SA-β-gal levels and the remarkable expansion of effector memory subclusters in CD4⁺ T cells. Moreover, senescent Lxrβ^−/− CD4⁺ T cells secreted elevated levels of proinflammatory cytokines, especially in effector memory populations, exhibiting a pronounced proinflammatory phenotype. RNA-sequencing further confirmed the role of LXRβ in restricting CD4⁺ T cell senescence. Mechanistically, the absence of LXRβ in CD4⁺ T cells directly enhanced senescence by promoting the cGAS/STING pathway. Blocking STING signaling with a targeted inhibitor significantly alleviated senescence in Lxrβ^−/− CD4⁺ T cells. Conclusions: Our findings demonstrate the role of LXRβ in regulating intestinal CD4⁺ T cell senescence to inhibit colitis development, identifying LXRβ as a potential therapeutic target for treating IBD. Full article

Background: Inflammatory Bowel Disease (IBD) involves a complex interplay between immune dysregulation and intestinal barrier failure. Traditional views focused on individual cell death pathways, but the emerging concept of PANoptosis—a coordinated inflammatory cell death involving apoptosis, necroptosis, and pyroptosis—offers a more holistic understanding of IBD pathogenesis. Objective: This review evaluates the role of PANoptosis in IBD, identifies key molecular triggers (such as the ZBP1-ADAR1 axis), and discusses the therapeutic potential of targeting this process. Methods: We analyzed recent literature and clinical trial data regarding programmed cell death (PCD) inhibitors and natural compounds in IBD models. Results: Preclinical data suggest that targeting PANoptotic regulators like RIPK1 and ZBP1 can restore barrier integrity. However, clinical translation remains challenging; for instance, while targeting pyroptosis via IL-1/IL-18 (Anakinra) showed promise in theory, clinical results in IBD have been disappointing. Furthermore, RIPK1 inhibitors such as GSK2982772 have failed to meet primary endpoints in Phase 2 trials. Conclusions: PANoptosis is a “hot” therapeutic target, but successful treatment likely requires combination therapies or “PANoptosome” specific modulators rather than single-pathway inhibition. Full article

Inflammatory Bowel Diseases (IBD), most notably ulcerative colitis (UC) and Crohn’s disease (CD), are long-standing disorders driven by dysregulated immune responses within the gastrointestinal tract and characterized by several metabolic disturbances, which are believed to influence disease progression. We have recently shown that a systemic deficiency of taurine, a semi-essential amino acid with anti-inflammatory properties, marks IBD. To characterize the temporal dynamics and determinants of taurine deficiency in IBD, we conducted a prospective longitudinal study assessing serum taurine levels in a cohort of 47 patients with IBD compared with 33 healthy controls. Serum taurine concentrations were measured at baseline and after a median follow-up period of 45 months using ELISA. Patients were stratified by disease subtype (UC and CD), age group, and clinical activity status at baseline and follow-up. Serum taurine levels were significantly lower in IBD patients at both baseline and the end of follow-up (p < 0.05), and remained stable over time within the CD and UC cohorts. In healthy individuals, but not in IBD patients, taurine concentrations declined with age, suggesting that age-related metabolic regulation of taurine is altered in the context of chronic intestinal inflammation. Stratification by disease activity revealed that taurine deficiency was present in both active and inactive IBD, particularly among younger patients, and differences between active and inactive disease were minimal. These findings indicate that the persistent reduction in serum taurine in IBD is independent of age, disease subtype, or clinical activity, and remains relatively constant over time across most patient subgroups, suggesting an underlying alteration in taurine metabolism or homeostasis associated with IBD pathophysiology. Further investigation is needed to elucidate the mechanisms linking taurine dysregulation to IBD progression. Full article