Search Results (4,634)

Background/Objectives: Gut microbiota dysbiosis is a key driver of inflammatory bowel disease (IBD), and fecal microbiota transplantation (FMT) has emerged as a potential therapeutic strategy. In this study, we investigated the protective effects of toddler-derived FMT against colitis and elucidated the underlying mechanisms. Methods: Firstly, fecal microbiota from healthy toddlers was transplanted into antibiotic-pretreated mice, establishing stable colonization between days 14 and 21 post-transplantation. Results: In a dextran sulfate sodium-induced colitis model, FMT significantly ameliorated colitis symptoms, including reduced disease activity index and restored colon length. Toddler-derived FMT improved the intestinal barrier by preserving goblet cell density and enhancing MUC2 expression. Meanwhile, colonic inflammation was alleviated by FMT, which suppressed pro-inflammatory cytokines, reduced CD4⁺ T cell counts, and associated with downregulation of JAK/STAT-related transcripts. 16S rRNA sequencing revealed that FMT remodeled the gut microbiota by enriching beneficial genera, including Bacteroides, Parabacteroides, Blautia, and Akkermansia, which correlated positively with colon length and negatively with inflammatory markers. Conclusions: These findings provided a theoretical foundation that toddler-derived microbiota represents a potential donor source for FMT in IBD. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory condition resulting from complex interactions between the immune system, genetic predisposition, and the gut microbiota. In this context, Escherichia coli (E. coli) plays a dual role in the human gut, ranging from harmless commensal strains to pathobionts capable of promoting intestinal inflammation. A growing body of evidence suggests that specific E. coli pathotypes, such as adherent-invasive E. coli (AIEC) and diffusely adherent E. coli (DAEC), contribute to the development and progression of IBD. This narrative review critically examines the microbiological, immunological, and clinical evidence supporting the role of E. coli in IBD, with particular emphasis on mechanisms of mucosal colonization, host–microbe interactions, and persistence within the inflamed intestinal environment. Furthermore, the lack of a standardized operational definition and the limited reproducibility of the AIEC phenotype are addressed, as well as uncertainty about the role played by E. coli as a primary initiator of the disease or as an opportunistic amplifier of intestinal inflammation, and the varying strength of evidence supporting associations with Crohn’s disease versus ulcerative colitis. Diagnostic implications, antimicrobial resistance, and therapeutic aspects are addressed as downstream and context-dependent consequences of E. coli–host interactions, with relevance for disease management and therapeutic response in patients with established IBD. By integrating data from experimental models, clinical studies, and translational research, the review identifies areas of consensus, ongoing controversy, and major knowledge gaps in IBD pathophysiology and clinical practice. Full article

Inflammatory bowel diseases, particularly ulcerative colitis (UC), are chronic relapsing inflammatory disorders with limited therapeutic options. The zinc-finger transcription factor ZBTB4 has been implicated in the initiation and progression of cancer, but its role in UC remains unknown. Here, we found that ZBTB4 deficiency exacerbates dextran sulfate sodium (DSS)-induced colitis in C57BL/6J male mice. Compared with the wild type, ZBTB4 deficiency increases weight loss, colon shortening and proinflammatory cytokine production. RNA-seq analysis revealed that ZBTB4 deficiency enhances Serpine1 expression and activates the NF-κB pathway. NF-κB inhibition by JSH-23 alleviated the effect of ZBTB4 deficiency on DSS-induced colitis. These results imply the protective role of ZBTB4 in UC. Through an integrated drug screening, we identified a natural sesquiterpene lactone, handelin, as a potential compound to enhance ZBTB4 expression in NCM460 cells. Handelin administration relieved colitis in wild-type mice but produced no effect in ZBTB4 knockout mice, demonstrating that its anti-colitic effect depends on ZBTB4 expression. Collectively, our results indicate the key role of ZBTB4 in UC and ZBTB4 agonists may serve as a novel approach for UC treatments. Full article

Inflammatory bowel diseases (IBDs) are diseases of chronic inflammation and intestinal epithelial cell (IEC) death that affect an estimated 7 million people worldwide. Intestinal barrier restoration is the most important determinant of remission in IBD, yet there are very few existing therapies that protect IECs from damage or support epithelial repair. The goal of this study was to develop a model system and tools that can be used to identify therapeutics that promote IEC survival in IBD. We developed a Beclin-1 cleavage reporter (BICR) that detects calpain-mediated Beclin-1 cleavage and the switch from autophagy to programmed cell death. We modified BICR with the HIV Tat peptide (BICR-Tat) and tested it in a model of live bacterial stress using commensal E. coli and IEC. BICR sensitively and specifically detected calpain activity in cell-free assays, and BICR-Tat successfully detected Beclin-1 cleavage and autophagy failure in IEC. Achieving IEC survival in the microbe-challenged IBD gut would be an important advance toward intestinal barrier restoration in this intractable disease. The BICR-Tat reporter coupled with the model of microbial stress developed in this study could enable high-throughput screening approaches to identify therapeutics with the potential to achieve barrier healing and sustained remission in IBD. Full article

Alterations in the intestinal microbiota have been implicated in both irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). However, their biological significance and therapeutic implications differ substantially between the two conditions. Although dysbiosis is a common feature, the mechanisms by which alterations in the microbiota contribute to disease pathophysiology and clinical expression are distinct. Some pathways are more prominent in IBS (e.g., the gut–brain axis), whereas others are more prominent in IBD (e.g., reduced microbial diversity). Equally important are pathways that appear to play a role exclusively in IBD [e.g., Adherent-invasive Escherichia coli (AIEC) and Paneth cells], as well as others that seem to be specific to IBS (e.g., mast cell activation). In IBD, microbiota changes are primarily linked to immune dysregulation, mucosal barrier impairment, and inflammation-driven pathways, whereas in IBS, they are mainly associated with functional disturbances mediated by neuroimmune signaling and microbial metabolites. Furthermore, several microbiome-associated biomarkers differ between these two diseases, and some are already assessed by international guidelines. Although the microbiota plays a key role in IBS and IBD pathophysiology, microbiome-based treatments remain limited, especially in IBD. There are clinically available treatments in IBS (e.g., rifaximin, low-FODMAP diet), but in IBD, only the probiotic VSL#3 is guideline-approved in ulcerative colitis pouchitis prophylaxis. Nevertheless, the dynamic nature of the microbiota continues to support the investigation of already studied (e.g., probiotics, fecal microbiota transplantation) and potential novel therapeutic approaches at the research level. The aim of this review is to compare the gut-microbiota-related pathophysiological pathways and biomarkers between IBS and IBD, to summarize the microbiome-related medications that have already been studied in both diseases, and to suggest new potential therapeutic options based on the gut microbiota. Full article

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

Boswellic acids (BAs), the major bioactive constituents of Boswellia serrata oleo–gum resin, exhibit well-documented anti-inflammatory and antioxidant activities, which correspond to their healing effects in arthritis, inflammatory bowel disease, asthma, metabolic syndrome, liver disorders, and certain cancers. However, their therapeutic potential is hindered by their poor aqueous solubility, low intestinal absorption, extensive metabolism, and overall low oral bioavailability. This review provides a comprehensive analysis of conventional Boswellia serrata products and advanced drug delivery systems designed to enhance the biological performance of BAs. We summarize recent developments in formulation strategies, including phytosomes, micelles, self-emulsifying drug delivery systems, solid lipid particles, polymeric nanoparticles, hydrogels, cyclodextrin complexes, metal-based nanocarriers, and hybrid delivery platforms. Available in vivo and cellular studies are critically evaluated, with a focus on disease-specific outcomes. Results indicate that emerging formulation technologies significantly increase the oral absorption, systemic exposure, and biological effectiveness of BAs. However, despite promising preclinical data, challenges remain regarding the standardization of Boswellia extracts, the stability of novel formulations, their safety, and limited clinical evaluation. By comparing the advantages and limitations of conventional preparations with modern drug delivery systems, this review outlines the most effective strategies to enhance the bioavailability of BAs and highlights future research directions for their translational development. Full article

Background/Objectives: Histologic mucosal healing is an increasingly recognized therapeutic target in inflammatory bowel disease (IBD), yet reliable non-invasive correlates remain limited. This study aimed to evaluate circulating cytokine patterns as detectability-based immune signals across the spectrum of histologic disease activity. Methods: In this prospective cross-sectional study, 59 patients with IBD and 36 healthy controls were enrolled. Serum interleukin-10 (IL-10) and interleukin-23 (IL-23) were quantified by ELISA. Histologic activity was graded using the Geboes score. Associations were assessed using non-parametric methods and multivariable logistic regression with Firth penalization. Results: IL-10 demonstrated apparent separation across histologic states, primarily driven by reduced detectability in active inflammation, and was inversely associated with histologic severity. IL-10 remained associated with histologic status, although estimates should be interpreted cautiously. Detectable IL-23 was confined to moderate-to-severe inflammation and did not show graded discrimination, with interpretation limited by the small number of detectable observations. Conclusions: IL-10 and IL-23 exhibit complementary patterns, reflecting detectability-based regulatory signaling and a severity-dependent inflammatory threshold, respectively, without evidence of independent clinical utility for IL-23 in the present dataset. These findings are exploratory and require validation in larger prospective cohorts. Full article

Background: Oral colon-targeted delivery for inflammatory bowel disease (IBD) faces significant challenges, including limited gastrointestinal stability, premature drug release, and insufficient mucosal retention. Methods: To address these limitations, a mucoadhesive polysaccharide-based composite hydrogel incorporating prednisolone-loaded polymeric micelles was developed to enhance colonic delivery and promote mucosal repair. Amphiphilic oxidized dextran–oleylamine (ODEX-OA) copolymers were synthesized to self-assemble into prednisolone-loaded micelles. These micelles were subsequently embedded within a thiolated chitosan (CSSH) hydrogel through a Schiff base reaction, yielding the ODEX-OA-Pred-CSSH composite. The resulting system was comprehensively characterized for particle size, mucoadhesion, degradation, and pH/ROS dual-responsive drug release. Its colon-targeting capability and therapeutic efficacy were subsequently assessed in a dextran sulfate sodium (DSS)-induced colitis mouse model. Results: In vitro, the composite hydrogel demonstrated nanoscale micellar size, enhanced drug release kinetics under simulated inflammatory colonic conditions, and prolonged colonic retention for up to 24 h following oral administration. In vivo, studies confirmed that ODEX-OA-Pred-CSSH significantly alleviated colitis, evidenced by a reduced disease activity index, diminished pro-inflammatory cytokine levels, restored colon length, decreased spleen index, and improved histological mucosal repair. Conclusions: These findings collectively suggest that this mucoadhesive micelle–hydrogel composite represents a promising and effective oral colon-targeted platform for the treatment of IBD. Full article

Essential oils (EOs) and their bioactive constituents have attracted growing interest as potential anticancer agents because they can target multiple pathways involved in tumor progression. However, the literature on their anticancer activity is highly heterogeneous and often limited by methodological weaknesses that reduce the reliability and translational value of the reported findings. This systematic review critically assessed the anticancer activity of EOs and EO-derived compounds by considering only studies that met defined methodological criteria. A PubMed search identified 872 articles published between 2015 and 2026, of which 97 were retained after screening based on EO chemical characterization, evaluation of cancer selectivity using non-tumoral control cells, and direct assessment of EO-driven anticancer effects. Across different tumor models, EOs and their constituents consistently showed selective cytotoxic or antiproliferative activity, commonly associated with oxidative stress, mitochondrial dysfunction, apoptosis, cell-cycle arrest, and modulation of oncogenic pathways. Some studies also reported reduced migration, invasion, and tumor-promoting signaling, while nanoformulation improved stability and efficacy in selected models. Overall, despite encouraging preclinical evidence, the translational potential of EO-based anticancer strategies remains limited by recurrent methodological shortcomings and insufficient in vivo validation. Standardized experimental criteria will be essential to improve reproducibility and support future clinical development. Full article

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

Background/Objectives: This study aimed to determine the incidence of herpes zoster (HZ) and risk factors associated with its occurrence in patients receiving Janus kinase inhibitors (JAKis) for immune-mediated inflammatory diseases (IMIDs), while evaluating preventive strategies and zoster vaccine uptake. Methods: We conducted a retrospective single-center cohort study including patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease, atopic dermatitis and alopecia areata treated with upadacitinib, baricitinib or tofacitinib. The primary outcome was incident HZ during JAKi exposure. Incidence rates (IRs) were calculated per 100 person-years (PY) and Cox regression identified factors associated with HZ. Results: A total of 292 patients contributed 565.5 PY of JAKi exposure. During follow-up, 23 patients (7.9%) developed HZ, corresponding to an overall IR of 4.07/100 PY (95% CI 2.40–5.73). Incidence rates were numerically lower with upadacitinib and varied across disease groups; differences were not statistically significant. Diabetes mellitus (HR 3.05, 95% CI 1.28–7.29) and chronic kidney disease (HR 3.24, 95% CI 1.17–8.95) were independently associated with HZ. Herpes simplex infection requiring systemic antiviral therapy was more frequent among patients who developed HZ. Recombinant zoster vaccine (RZV) uptake was low (9.9%), but higher among patients evaluated in a dedicated infectious risk consultation. No HZ events were observed among RZV-vaccinated patients. Although six HZ events (26.1%) were severe, all cases resolved completely. Conclusions: HZ remains a relevant complication of JAKi therapy across IMIDs. Diabetes mellitus and chronic kidney disease may help identify higher-risk patients, while structured infectious risk assessment could improve vaccine uptake. Full article

Ulcerative colitis is a chronic inflammatory bowel disease that requires new treatment approaches beyond traditional anti-inflammatory drugs. In this study, we analyzed publicly available single-cell RNA sequencing data from a DSS-induced colitis mouse model and identified pyroptosis as a key biological process linked to epithelial damage. Based on this, we screened marine-derived brominated indoles for potential pyroptosis inhibitors and identified 6-bromoindole-3-acetonitrile as a promising candidate. Our results show that this compound significantly alleviates DSS-induced colitis in mice, with notable body weight recovery and a drop in Disease Activity Index (DAI) scores from about 8.5 to below 4 (p < 0.05). At the molecular level, it lowers the mRNA levels of Nlrp3, Caspase-1, and other pyroptosis-related genes, indicating suppression of the pyroptotic pathway. Moreover, treatment helps restore the intestinal barrier by supporting goblet cell regeneration and strengthening tight junctions. Molecular docking suggests that 6-bromoindole-3-acetonitrile binds stably to the active site of myeloperoxidase (MPO), with a binding energy of −18.1 kcal/mol, offering a possible structural basis for its anti-inflammatory effects. Together, these findings point to a marine-derived compound that reduces both inflammation and pyroptosis, representing a promising strategy for treating ulcerative colitis. Notably, these results come from preclinical studies and need further validation in clinical settings. Full article

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), represents a chronic immune-mediated disorder frequently associated with extraintestinal manifestations. While musculoskeletal, dermatologic, and ocular complications are well recognized, ear, nose, and throat (ENT) involvement remains underrecognized despite its potential morbidity. Objective: To systematically evaluate the spectrum of ENT manifestations in IBD, focusing on clinical presentation, diagnostic approaches, and outcomes. Methods: A systematic literature search was conducted in PubMed and Scopus in accordance with PRISMA 2020 guidelines. Eligible studies included English-language human studies (2015–2026) reporting ENT manifestations in UC or CD. Following screening, 23 studies were included in the qualitative synthesis. Extracted data comprised study design, IBD subtype, patient demographics, ENT manifestations, diagnostic methods, and clinical outcomes. Results: The majority of studies consisted of case reports and small observational series. Sensorineural hearing loss (SNHL) was the most frequently reported manifestation in both adult and pediatric populations, with evidence suggesting immune-mediated mechanisms and variable responsiveness to corticosteroids. Nasal involvement included pyoderma gangrenosum, pyoderma vegetans, and aseptic nasal septal abscess, occasionally resulting in severe structural complications such as saddle-nose deformity. Laryngeal and airway involvement included dysphonia, tracheitis, and rare but potentially life-threatening inflammatory airway disease. Additional findings included associations with chronic rhinosinusitis. Diagnosis relied on audiometry, imaging, endoscopy, and histopathology. Systemic corticosteroids were frequently effective; however, delayed recognition may lead to irreversible sequelae. Conclusions: ENT manifestations in IBD constitute a clinically heterogeneous but important group of extraintestinal complications. Increased awareness of ENT manifestations may support earlier diagnosis and multidisciplinary management of IBD, potentially reducing irreversible complications. Full article

Muscle wasting contributes substantially to inflammatory bowel disease (IBD)-related disability, but its association with colitis severity across disease stages remains poorly characterized. We therefore assessed skeletal muscle mass, fiber morphology, and voluntary wheel-running performance in Winnie mice—a spontaneous Muc2 mutant model of chronic colitis—in separate female and male homozygous mutant and WT littermate cohorts. Assessments were performed at 5 weeks, before overt colitis, and at 15 weeks, in a cohort with more pronounced colitis. Outcomes included disease activity index (DAI), fecal lipocalin-2 (LCN-2), wheel-running metrics, soleus and tibialis anterior mass, and minimal Feret’s diameter distributions. At 5 weeks, Winnie mice showed no overt disease activity and no consistent structural muscle deficit. In contrast, the 15-week cohort exhibited marked colitis in both sexes, with increased DAI and LCN-2, reduced voluntary wheel-running performance, lower soleus and tibialis anterior mass, and smaller muscle fiber diameters with left-shifted size distributions. Correlation analyses identified associations between fecal LCN-2, skeletal muscle mass and size, and wheel-running distance and velocity, supporting a link between intestinal inflammation and muscle impairment in this model. These cross-sectional data are consistent with reduced voluntary activity and structural myopathy during progression of spontaneous colitis. The Winnie mouse model therefore provides a clinically relevant preclinical platform to study IBD-associated muscle wasting and its association with intestinal inflammation. Full article