Search Results (349)

Inflammatory bowel diseases (IBDs) encompass Crohn’s disease and ulcerative colitis. They represent idiopathic and chronic inflammatory conditions. Mucosal immune dysfunction and compromised gastrointestinal barrier integrity are implicated in the pathophysiological mechanisms of inflammatory bowel diseases. Recent studies have identified endothelial dysfunction as a pivotal mediator in IBD pathogenesis. Through multiple cellular and molecular interactions, endothelial dysfunction orchestrates inflammatory responses. Objectives: This systematic review examines contemporary evidence (2019–2025), emphasising the role of endothelial dysfunction in intestinal inflammation mechanisms, focusing on vascular-epithelial crosstalk, molecular signalling pathways, and therapeutic implications. Methods and results: A comprehensive literature search was conducted using PubMed, Google Scholar, Europe PMC and DOAJ databases, focusing on peer-reviewed articles published between 2019 and 2025. Following the database search and screening process, a total of 53 studies met the eligible criteria and were included in the final analysis. Keywords included “endothelial dysfunction,” “inflammatory bowel disease,” “gut-vascular barrier,” “nitric oxide,” and “intestinal inflammation.” Contemporary research demonstrates that endothelial dysfunction in IBD manifests through decreased nitric oxide bioavailability, enhanced oxidative stress, aberrant cytokine networks, pathological angiogenesis, and compromised gut-vascular barrier integrity. The emerging concept of dual barrier dysfunction highlights the interdependent relationship between epithelial and endothelial barriers in maintaining intestinal homeostasis. Conclusions: Offering novel therapeutic targets for precision medicine approaches, endothelial dysfunction represents a central driver in the pathophysiological mechanism in IBD. Understanding vascular-epithelial interactions provides fundamental insights for developing targeted interventions to restore intestinal barrier function and resolve chronic inflammation. Full article

Irritable Bowel Syndrome (IBS) is one of the most prevalent gastrointestinal disorders, affecting about 11% of the global population and exerting a substantial burden on quality of life and healthcare systems. Despite the emerging interest in this disease, its pathophysiology remains elusive, reflecting the interplay between the brain–gut axis, neuroendocrine dysregulation, immune activation, barrier dysfunction, microbial imbalance, and environmental triggers. Disruptions in the hypothalamic–pituitary–adrenal axis, impaired serotonin signaling, bile acid malabsorption, and altered intestinal permeability collectively result in the emergence of abnormal motility, visceral hypersensitivity, and chronic inflammation. The gut microbiome further modulates these processes by influencing neurotransmitter metabolism, immune responses, and epithelial integrity, positioning it as both a driver of symptoms and a promising therapeutic target. The aim of this review is to synthesize current mechanistic insights into IBS, highlighting the interconnected roles of the brain–gut axis, immune modulation, and microbial dynamics, and to explore how these pathways may be translated into precision medicine approaches. This review integrates molecular, microbial, and neuroimmune perspectives to propose a systems-level understanding of IBS pathophysiology and its implications for precision medicine. By integrating host–microbe interactions, dietary influences, and genetic predispositions, we highlight the mechanistic complexity underlying IBS and the potential for translating these insights into personalized strategies for symptom control and improved quality of life. Full article

Natural bioactive chemicals sourced from marine species have attracted growing interest due to their immunomodulatory, antioxidant, and gut microbiota-regulating characteristics. These chemicals, especially peptides, offer therapeutic approaches for addressing inflammation, immunological dysfunction, and intestinal barrier disturbance, which are frequently observed in conditions such as inflammatory bowel disease (IBD). This review centers on current discoveries about marine-derived peptides from octopus, sea conch, and scallop. These substances have demonstrated a considerable ability to restore intestinal integrity, regulate immune cell function, reduce pro-inflammatory cytokines, and rebalance dysbiotic gut microbiota. We consider several in vivo scenarios, encompassing dextran sulphate sodium (DDS)-induced colitis and cyclophosphamide-induced immunosuppression. These compounds raise the expression of tight junction proteins (including ZO-1 and occludin), boost the production of mucin, and encourage the growth of good bacteria such as Lactobacillus and Lachnospiraceae. Their effects are mechanistically associated with the inhibition of critical inflammatory pathways (e.g., Nuclear factor-κB (NF-κB), Toll-like receptor 4 (TLR-4)) and the modulation of both innate and adaptive immune responses. These versatile bioactives can serve as dietary supplements or complementary therapies for gastrointestinal and cancer-related issues. This review emphasizes the therapeutic potential of marine peptides, concentrating on gut–immune–microbiota interactions, as well as exploring future avenues for clinical translation and drug development Full article

Background: Pelvic autonomic nerve injury during colorectal surgery causes debilitating urinary, bowel, and sexual dysfunction. This review synthesizes contemporary evidence on neuroanatomy, nerve-sparing techniques, and functional outcomes to minimize iatrogenic injury while maintaining oncologic efficacy. Methods: Systematic analysis of cadaveric studies, clinical trials, and imaging advancements focused on the superior hypogastric plexus, hypogastric nerves, pelvic splanchnic nerves (S2–S4), and inferior hypogastric plexus. Surgical innovations evaluated included robotic-assisted dissection, fluorescence-guided visualization, and intraoperative neuromonitoring. We distinguished evidence for nerve identification from evidence for functional protection and graded study designs accordingly. Results: Anatomical variability (e.g., superior hypogastric plexus leftward deviation 58.8%; hypogastric nerve median width 3.5 mm) necessitates precision techniques. Nerve-sparing approaches reduce urinary dysfunction from 30–70% to 10–30% and sexual dysfunction from 40–80% to 15–30%. However, the functional benefit of specific technical steps is often derived from anatomical rationale and cohort studies, with limited randomized trials for individual maneuvers. While technique refinements such as Denonvilliers’ fascia preservation may offer early sexual function benefits, randomized evidence shows no 12-month urinary advantage and uncertainty regarding longer-term durability; routine adoption should be individualized. Advanced imaging (3 T MRI, diffusion tensor imaging) and fluorescence guidance improve pre-/intraoperative visualization, but randomized evidence for improved postoperative urinary or sexual function is limited. Randomized data support pelvic intraoperative neuromonitoring in reducing urinary deterioration; most adjuncts have observational or feasibility-level support. Conclusions: Integrating neuroanatomical knowledge with advanced technologies enhances identification and may support nerve-sparing execution; however, robust randomized evidence for durable functional protection of novel technologies and specific technical steps remains limited. Priorities include standardizing preservation protocols, conducting randomized trials that validate the efficacy of individual surgical maneuvers, linking identification to functional outcomes, and validating long-term patient-reported outcomes. Full article

Micro- and nanoplastics (MNPs) are emerging environmental immunotoxins with widespread human exposure through ingestion, inhalation, and dermal contact. Detected in the placenta, lungs, blood, bone marrow, and brain, MNPs accumulate in immune organs where they disrupt innate and adaptive cell functions. This review aims to provide a comprehensive summary of the current knowledge on how MNPs affect the immune system at the cellular and molecular levels. Experimental evidence shows that MNPs impair macrophage phagocytosis, skew dendritic cell maturation, trigger neutrophil extracellular traps, and alter T and B cell responses. Mechanistically, these effects are driven by oxidative stress, mitochondrial dysfunction, and activation of key inflammatory signaling pathways, including NF-κB, MAPK, and NLRP3 inflammasome, leading to apoptosis, pyroptosis, and chronic low-grade inflammation. Furthermore, MNP-induced disruption of epithelial barriers and gut microbiota composition undermines immune tolerance and contributes to the pathogenesis of autoimmune conditions. Preclinical models provide evidence linking MNP exposure to exacerbation of diseases such as systemic lupus erythematosus, inflammatory bowel disease, and rheumatoid arthritis. However, human epidemiological data remain limited, highlighting the urgent need for standardized exposure protocols, advanced omics technologies, and longitudinal cohort studies are urgently needed to establish causal links and inform public health strategies. Full article

Background/Objectives: The aim of this study was to investigate the experiences of Swedish patients with inflammatory bowel disease (IBD) regarding intimacy and sexuality-related issues, and to explore both patients’ and healthcare professionals’ perspectives on discussing these topics. Methods: This cross-sectional cohort study used two internet-based questionnaires: one targeting patients and the other healthcare professionals. The patient survey examined the impact of IBD and its treatment on relationships and sexuality, as well as expectations on healthcare support. The survey of healthcare professionals focused on experiences of discussing sexuality-related topics with IBD patients. Responses were analyzed using both quantitative and content analysis. Results: A total of 556 IBD patients and 118 healthcare professionals responded. Among patients, 78% reported difficulties related to relationships and sexuality, with physical symptoms like pain, fecal urgency, and bloating, and psychological problems such as fear of leakage and reduced sexual desire. Over half wished for these issues to be addressed in routine care, yet 84% had never initiated such discussions themselves. Among healthcare professionals, 23% never addressed issues of relationship and sexuality with patients, and another 50% did so only occasionally. Only 15% had access to qualified sexologists for referrals, and just 8% offered sexual rehabilitation after pelvic surgery. Conclusions: Sexual health is frequently compromised in IBD patients, especially in women, but remains insufficiently addressed in clinical practice. Both patients and healthcare professionals expressed a need for more open discussions about relationships and sexuality. Improving care requires routine screening, multidisciplinary support, and the development of guidelines for managing sexual dysfunction in IBD. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent condition worldwide, occurring both independently and, more importantly, as the most common extraintestinal complication of inflammatory bowel disease (IBD). The study primarily investigated MASLD prevalence in Crohn’s disease (CD) and ulcerative colitis (UC) to enhance prevention and early detection, especially given the recent approval of the first treatment for this condition. Secondary objectives included identifying risk factors, exploring the uric acid/high-density lipoprotein cholesterol ratio (UHRatio) as a steatosis marker and evaluating correlations between non-invasive fibrosis scores, Fibrosis-4 (FIB-4), AST-to-Platelet Ratio Index (APRI), and histological fibrosis severity. We conducted a prospective study on 58 patients diagnosed with IBD. The type of IBD was not independently associated with liver steatosis or fibrosis. Disease activity correlated significantly with hepatic steatosis in CD patients and with hepatic fibrosis in UC patients. The UHRatio proved useful in assessing steatosis prevalence, whereas FIB-4 and APRI scores did not correlate significantly with fibrosis severity. This study is, to our knowledge, the first to evaluate UHRatio as a potential predictor of MASLD in patients with IBD, expanding on previous findings reported in the general population. Our results suggest that this non-invasive biomarker, previously used to identify MASLD, may improve early prediction and could serve as a useful screening tool for MASLD in IBD patients. Full article

Background/Objectives: Psychological stress is a main factor in the pathophysiology of irritable bowel syndrome (IBS) and contributes to changes in gastrointestinal motility and inflammatory responses. We investigated the effects of three probiotic strains, Lactobacillus brevis N1, L. brevis N2, and Bacillus amyloliquefaciens S1, isolated from Korean fermented foods, on stress-induced colonic hypermotility and inflammatory signaling in a rat model. Methods: Thirty female Wistar rats were divided into five groups: Control (sham), Stress (water avoidance stress, WAS), Treatment A (WAS + L. brevis N1), Treatment B (WAS + L. brevis N2), and Treatment C (WAS + B. amyloliquefaciens S1) (n = 6 per group). Rats were exposed to WAS for 1 h daily for nine consecutive days. Furthermore, before stress exposure, probiotics were administered by oral gavage. The fecal pellet output (FPO), body weight, and food intake were recorded daily. Colon tissues were harvested for protein extraction, and inflammatory signaling was evaluated by Western blotting for NF-κB and IκBα, with β-actin as loading control. Immunoreactive bands were visualized by enhanced chemiluminescence (ECL) and quantified using ImageJ software version 1.54k. Results: The WAS group showed significantly higher FPO than the sham group (p < 0.01). FPO was significantly decreased in rats treated with L. brevis N2 compared to that in the WAS-only group (p < 0.05). Additionally, immunohistochemical analysis revealed that NF-κB expression was suppressed in all the probiotic groups. Conclusions: Therefore, probiotics are suggested to have elevated anti-inflammatory effects through the downregulation of the NF-κB signaling pathway by restoring IκBα expression and can be utilized as potential therapeutics for stress-induced gastrointestinal dysfunction. Full article

Psychological and motivational factors are implicated in various medical conditions, yet the link between physical health and life aspirations, as defined in Self-Determination Theory (SDT), remains underexplored. To address this gap and advance theory, we conducted a preliminary investigation of associations between aspirations and self-reported symptoms across five functional medical conditions—gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), headaches, sleep disturbances, and sexual dysfunction. We surveyed 392 Canadian medical patients (Mage = 42.8 years, SD = 12.7, 50.5% women, 82.1% white, 75.3% with higher education) to assess whether the relative importance, likelihood, and attainment of intrinsic (e.g., personal growth, relationships, community, health) and extrinsic (e.g., wealth, fame, image) aspirations were associated with symptoms. Consistent with hypotheses, greater relative prioritization of intrinsic goals was linked to fewer symptoms—especially sleep disturbance—while extrinsic aspirations were associated with increased symptoms, particularly GERD. Sociodemographic factors, such as age, gender, education, religiosity, and subjective financial status, also showed associations with goal orientations and symptom burden, broadly aligning with SDT predictions. Findings highlight the potential relevance of people’s personal goals in patient-centered care for functional conditions and underscore the need for further research exploring mechanisms and moderators of these effects. Full article

Fusobacterium nucleatum is a Gram-negative anaerobe that occupies a central ecological niche in oral biofilms but has emerged as a trans-compartmental pathogen implicated in gastrointestinal and cardiovascular diseases. In inflammatory bowel diseases, Fusobacterium nucleatum adheres to the intestinal epithelium via adhesins such as FadA, disrupts tight junctions, and induces Toll-like receptor–mediated inflammatory cascades, amplifying epithelial permeability and sustaining mucosal inflammation. In colorectal cancer, Fusobacterium nucleatum promotes carcinogenesis through multiple mechanisms, including β-catenin activation, modulation of oncogenic microRNAs, and immune evasion via Fap2–TIGIT signaling, while also fostering a pro-inflammatory and immunosuppressive tumor microenvironment. Its enrichment correlates with advanced tumor stage, chemoresistance, and poor prognosis, underscoring its potential as a biomarker and therapeutic target. Beyond the gut, Fusobacterium nucleatum has been detected in atherosclerotic plaques and endocardial tissues, where it contributes to endothelial dysfunction, foam cell formation, oxidative stress, and plaque instability, thereby linking chronic oral infection with cardiovascular risk. Collectively, evidence suggests that Fusobacterium nucleatum acts as a pathophysiological connector across IBD, CRC, and CVD through conserved mechanisms of adhesion, immune modulation, and inflammation. Understanding these processes provides opportunities for innovative interventions, ranging from targeted antimicrobials and host-directed therapies to dietary and microbiome-based strategies, aimed at mitigating the systemic burden of this organism and improving clinical outcomes across multiple diseases. Full article

Gut microbiota changes have emerged as central players in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and inflammatory bowel disease (IBD). Although these diseases affect distinct primary organs, they share converging mechanisms driven by dysbiosis, including loss of beneficial short-chain fatty acid-producing taxa such as Faecalibacterium prausnitzii and Roseburia, enrichment of pro-inflammatory Enterobacteriaceae, and disruption of bile acid and tryptophan metabolism. These shifts compromise epithelial barrier integrity, promote the translocation of microbial products such as lipopolysaccharide, and trigger toll-like receptor 4-mediated activation of inflammatory cascades dominated by tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta. In MASH, this dysbiotic environment fuels hepatic inflammation, insulin resistance, and fibrogenesis, while in IBD it sustains chronic mucosal immune activation. Shared features include impaired butyrate availability, altered bile acid pools affecting farnesoid X receptor and Takeda G protein-coupled Receptor 5 signaling, and defective aryl hydrocarbon receptor activation, all of which link microbial dysfunction to host metabolic and immune dysregulation. Understanding these overlapping pathways provides a deeper understanding of the role of the gut-liver and gut-immune axes as unifying frameworks in disease progression. This narrative review synthesizes current evidence on gut microbiota in MASH and IBD, underscoring the need for longitudinal, multi-omics studies and microbiome-targeted strategies to guide personalized therapeutic approaches. Full article

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract, characterized by dysregulated inflammatory responses throughout the gastrointestinal tract. It includes two major phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC), which present with varying gastrointestinal and systemic symptoms. The pathophysiology of IBD is multifactorial including genetic predisposition, mucosal and epithelial dysfunction, environmental injury, and both innate and adaptive immune response abnormalities. Several predisposing genetic factors have been associated with IBD explaining the strong hereditary risk for both CD and UC. For example, Caspase Recruitment Domain 9 (CARD9) variant rs10781499 increases risk for IBD, while other variants are specific to either CD or UC. CD is related to loss-of-function mutations in the nucleotide oligomerization domain containing the protein 2 (NOD2) gene and Autophagy-Related 16-like 1 (ATG16L1) gene. UC risk is increased particularly in Chinese populations by the A-1661G polymorphism of the Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene. This abnormal CTLA-4 interferes with B- and T-cell responses causing predisposition to autoimmune conditions. Previous studies suggested that IBD results from breakdown of the adaptive immune system, primarily of T-cells. However, new evidence suggests that a primary breakdown of the innate immune system in both CD and UC increases susceptibility to invasion by viruses and bacteria, with a compensatory overactivation of the adaptive immune system as a result. When this viral and microbial invasion continues, further damage is incurred, resulting in a downward cycle of further cytokine activation and epithelial damage. Released biomarkers also affect the permeability of the epithelial membrane, including lactoferrin, nitric oxide (NO), myeloperoxidase (MPO) and its activation of hypochlorous acid, matrix metalloproteinases (MMPs), especially MMP-9, omentin-1, and others. Increased macrophage and dendritic cell dysfunction, increased neutrophil activity, increased numbers of innate lymphoid cells, increased T-cells with decreased regulatory T-cells (Tregs), and changes in B-cell populations and immunoglobulin (Ig) functions are all associated with IBD. Finally, treatment of IBD has typically consisted of medical management (e.g., aminosalicylates and corticosteroids) and lifestyle modification, and surgical intervention in extreme cases. New classes of medications with more favorable side effect profiles include anti-integrin antibodies, vedolizumab, etrolizumab, and carotegrast methyl. Additionally, fecal microbiota transplant (FMT) is a newer area of research for treatment of IBD along with TNF-blockers, JAK inhibitors, and S1PR modulators. However, expense and long preparation time have limited the usefulness of FMT. Full article

Background: Inflammatory Bowel Disease (IBD), including Ulcerative Colitis and Crohn’s Disease, is a multifactorial inflammatory condition of the intestinal tract driven by a complex interplay of genetic factors, immune system dysfunction, and gut microbiota alterations. This review aims to synthesize current advancements in modern drug development strategies for IBD. It emphasizes the integration of computational modelling, cell-based experiments, and animal model studies to enhance translational outcomes. Methods: To compile this review, an extensive literature search was performed utilizing PubMed, Scopus, and Google Scholar databases for English-language research and review articles published between 2000 and 2025 using keywords such as “IBD,” “molecular docking,” “bioinformatics,” “organoids,” “animal models,” and “network pharmacology,” among others. A total of 199 peer-reviewed studies were identified for inclusion based on relevance, transparency, and methodological robustness. Results: The review outlines a range of cutting-edge approaches to IBD drug discovery. These include computer modelling, molecular docking, and network analysis to accelerate early-stage target prediction and drug screening. The review further highlights the critical importance of utilizing 2D and 3D cell culture systems in parallel with advanced animal models. It emphasizes the critical integration of computational predictions with biologically relevant in vitro and in vivo validations to improve the reliability and efficiency of drug development. Conclusions: The integration of computer modelling, cell culture systems, and animal studies provides a revolutionary paradigm for accelerating drug discovery to IBD and other diseases enabling personalized and more effective treatment approaches. Full article

Inflammatory bowel disease (IBD) demonstrates chronic relapsing inflammation extending beyond adaptive immunity dysfunction. “Trained immunity”—the reprogramming of innate immune memory in myeloid cells and hematopoietic progenitors—maintains intestinal inflammation; however, the mechanism by which gut microbiome orchestration determines protective versus pathological outcomes remains unclear. Microbial metabolites demonstrate context-dependent dual effects along the gut–bone marrow axis. Short-chain fatty acids typically induce tolerogenic immune memory, whereas metabolites like succinate and polyamines exhibit dual roles: promoting inflammation in certain contexts while enhancing barrier integrity in others, influenced by cell-specific receptors and microenvironmental factors. Interventions include precision probiotics and postbiotics delivering specific metabolites, fecal microbiota transplantation addressing dysbiotic trained immunity, targeted metabolite supplementation, and pharmacologic reprogramming of pathological myeloid training states. Patient stratification based on microbiome composition and host genetics enhances therapeutic precision. Future research requires integration of non-coding RNAs regulating trained immunity, microbiome–immune–neuronal axis interactions, and host genetic variants modulating microbiome–immunity crosstalk. Priorities include developing companion diagnostics, establishing regulatory frameworks for microbiome therapeutics, and defining mechanistic switches for personalized interventions. Full article

The rising global prevalence of inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis, is paralleled by an increased risk of colitis-associated colorectal cancer. Persistent intestinal inflammation promotes genetic instability and epigenetic reprogramming within epithelial and immune cells, driving the multistep transition from inflammation to neoplasia. This review integrates human and preclinical model evidence with literature mining and bioinformatic analyses of genetic, epigenetic, and ncRNA data to dissect molecular mechanisms driving colitis-associated colorectal cancer from chronic inflammation. We highlight how pro-inflammatory cytokines (e.g., TNF-α, IL-6), oxidative stress, and microbial dysbiosis converge on key transcriptional regulators such as NF-κB and STAT3, inducing DNA methylation and histone modifications (e.g., H3K27me3); altering chromatin dynamics, gene expression, and non-coding RNA networks (e.g., miR-21, MALAT1, CRNDE); ultimately reshaping pathways involved in proliferation, apoptosis, and immune evasion. This review updates new potential associations of entities with these diseases, in their networks of interaction, summarizing major aspects of genetic and chromatin-level regulatory mechanisms in inflammatory bowel disease and colorectal cancer, and emphasizing how these interactions drive the inflammatory-to-neoplastic transition. By underscoring the reversibility of epigenetic changes, we explore their translational potential in early detection, surveillance, and precision epigenetic therapy. Understanding the interplay between genetic mutations and chromatin remodeling provides a roadmap for improving diagnostics and personalized treatments in inflammatory bowel disease-associated colorectal carcinogenesis. Full article