Search Results (280)

Background/Objectives: The two major subtypes of inflammatory bowel disease (IBD)—Crohn’s disease (CD) and ulcerative colitis (UC)—are known to increase the likelihood of developing colorectal cancer (CRC). While this relationship has been well studied in Western populations, evidence from East Asia remains limited and inconsistent. Using nationwide cohort data, this study explored the potential connection between IBD and CRC in a large Korean population. Methods: We conducted a retrospective cohort study using data from the Korean National Health Insurance Service–National Sample Cohort from 2005 to 2019. A total of 9920 CRC patients were matched 1:4 with 39,680 controls using propensity scores based on age, sex, income, and region. Overlap weighting and multivariable logistic regression were used to evaluate the association between IBD and CRC. Subgroup analyses were conducted to assess effect modification by demographic and clinical factors. Results: IBD markedly increased the likelihood of developing CRC (adjusted odds ratio (aOR) = 1.38; 95% confidence interval (CI): 1.20–1.58; p < 0.001), with the association primarily driven by UC (aOR = 1.52; 95% CI: 1.27–1.83). CD appeared unrelated to heightened CRC risk overall, though a significant association was observed among low-income CD patients (aOR = 1.58; 95% CI: 1.15–2.16). The UC–CRC association persisted across all subgroups, including patients without comorbidities. Conclusions: Our findings support an independent association between IBD—particularly UC—and increased CRC risk in Korea. These results underscore the need for personalized CRC surveillance strategies that account for disease subtype, comorbidity burden, and socioeconomic status, especially in vulnerable subpopulations. Full article

Background/Objectives: Chronic inflammation and Western-style diets elevate colorectal cancer (CRC) risk, particularly in individuals with colitis, a feature of inflammatory bowel disease (IBD). Diets rich in polyphenol-containing functional foods, such as cocoa, may reduce gut inflammation and modulate the gut microbiome. This study investigated the impact of cocoa polyphenol (CP) supplementation on inflammation and microbiome composition in mice with colitis, fed either a healthy or Western diet, before, during, and after the onset of disease. We hypothesized that CPs would attenuate inflammation and promote distinct shifts in the microbiome, especially in the context of a Western diet. Methods: A 2 × 2 factorial design tested the effects of the basal diet (AIN93G vs. total Western diet [TWD]) and CP supplementation (2.6% w/w CocoaVia™ Cardio Health Powder). Inflammation was induced using the AOM/DSS model of colitis. Results: CP supplementation did not reduce the severity of colitis, as measured by disease activity index or histopathology. CPs did not alter gene expression in healthy tissue or suppress the colitis-associated pro-inflammatory transcriptional profile in either of the two diet groups. However, fecal microbiome composition shifted significantly with CPs before colitis induction, with persistent effects on several rare taxa during colitis and recovery. Conclusions: CP supplementation did not mitigate inflammation or mucosal injury at the tissue level, nor did it affect the expression of immune-related genes. While CPs altered microbiome composition, most notably in healthy mice before colitis, these shifts did not correspond to changes in inflammatory signaling. Basal diet remained the primary determinant of inflammation, mucosal damage, and colitis severity in this model. Full article

The gut microbiota has emerged as a key area of biomedical research due to its integral role in maintaining host health and its involvement in the pathogenesis of many systemic diseases. Growing evidence supports the notion that gut dysbiosis contributes significantly to diseases and their progression. An example would be inflammatory bowel disease (IBD), a group of conditions that cause inflammation and swelling of the digestive tract, with the principal types being ulcerative colitis (UC) and Crohn’s disease (CD). Another notable disease with significant association to gut dysbiosis would be colorectal cancer (CRC), a malignancy which typically begins as polyps in the colon or rectum, but has the potential to metastasise to other parts of the body, including the liver and lungs, among others. Concurrently, advances in nanomedicine, an evolving field that applies nanotechnology for disease prevention, diagnosis, and treatment, have opened new avenues for targeted and efficient therapeutic strategies. In this paper, we provide an overview of the gut microbiota and the implications of its dysregulation in human disease. We then review the emerging nanotechnology-based approaches for both therapeutic and diagnostic purposes, with a particular focus on their applications in IBD and CRC. Full article

Background/Objective: Immune checkpoint inhibitors (ICIs) are highly effective cancer therapies used across a broad spectrum of malignancies. They function by disrupting immune inhibitory pathways, resulting in an amplified immune response against tumors. However, this heightened immune activity can predispose patients to immune-mediated colitis (IMC), which is graded using the Common Terminology Criteria for Adverse Events (CTCAE) and can range from mild diarrhea to severe colitis. Prior studies have shown that fecal stream diversion can modify the gut microbiome and influence the severity of intestinal inflammation. This study investigates the impact of fecal stream diversion on IMC outcomes in cancer patients receiving ICIs. Methods: We conducted a retrospective cohort study of patients treated with ICIs from 2016 to 2023 who had a history of fecal stream diversion. Demographic, oncologic, and toxicity-related data were collected. Patients with active gastrointestinal infections, autoimmune GI diseases, or graft-versus-host disease were excluded. Descriptive statistics and univariate and multivariate logistic regression analyses were performed using SAS version 9.4. Results: A total of 44 patients were included and categorized into two groups based on the timing of bowel stoma creation relative to the IMC event. CTCAE grade for diarrhea was used to assess GI toxicity. While overall CTCAE grade distribution for diarrhea did not differ significantly between groups (p = 0.22), Hispanic ethnicity was significantly associated with a lower CTCAE grade compared to non-Hispanic or Latino individuals (OR [95% CI] = 0.12 [0.02, 0.62], p = 0.011). In contrast, higher CTCAE grades were significantly associated with ileostomy versus colostomy (OR [95% CI] = 3.21 [1.01, 10.18], p = 0.048) and in patients without an ostomy at the time of diarrhea onset compared to those with an ostomy (OR [95% CI] = 8.87 [2.51, 31.31], p = 0.0007). Conclusions: Our findings suggest that the CTCAE diarrhea grade is significantly associated with ethnicity, type of stoma, and presence of ostomy at the time of diarrhea. Limitations include the retrospective study design and small sample size. These results contribute to understanding potential strategies for mitigating the serious gastrointestinal toxicities of ICIs. Full article

Background/Objectives: Keratins form a crucial component of the epithelial cytoskeleton, playing an essential role in maintaining tissue architecture and coordinating key cellular functions. KRT80 is a type II keratin that has emerged as an oncogenic driver in several malignancies, yet its involvement in colorectal cancer (CRC) remains unclear. Here, we investigated the molecular interaction between miR-195-5p, KRT80 expression, and CRC growth. Methods: Potential miR-195-5p binding sites in the KRT80 3′-UTR were identified through the use of integrated bioinformatic analyses, while publicly available datasets confirmed a significant overexpression of KRT80 in CRC tissues compared to normal mucosa. This finding was further validated through the use of mRNA and protein analysis in paired tumor and adjacent normal samples from CRC patients. Results: Functional assays involving CRC cell lines showed that transfection with miR-195-5p mimics led to a significant downregulation of KRT80 expression, reflecting the effects of direct KRT80 silencing by siRNA. Both molecular approaches induced G₁-phase cell cycle arrest, concomitantly with reductions in G₂/M populations. Furthermore, the in vivo delivery of miR-195-5p mimics in a mouse model of colitis-associated CRC resulted in a significant reduction in Krt80 expression in the colon. Conclusions: Collectively, our results reveal that miR-195-5p negatively regulates KRT80 expression, contributing to its tumor-suppressive activity in colorectal cancer and highlighting a molecular mechanism with potential therapeutic relevance. Full article

Enterotoxigenic Bacteroides fragilis (ETBF) promotes colitis-associated cancer through the Bacteroides fragilis toxin (BFT), which induces colonic inflammation that can be exacerbated by external stimuli. We found that BALB/c mice infected with ETBF and treated with azoxymethane and dextran sodium sulfate (DSS) developed numerous distal colon polyps more rapidly than B6 mice, suggesting strain differences in ETBF-induced tumorigenicity. Using a bft gene-deficient ETBF strain, we confirmed BFT’s crucial role in ETBF-promoted tumorigenesis and inflammation. While both 1% and 2% DSS induced comparable polyp formation, 1% DSS minimized mortality, proving sufficient for maximizing polyp development. Mechanistically, BFT-mediated tumorigenesis involves NF-κB/CXCL1 signaling in colonic epithelial cells exposed to BFT and DSS, a pathway known to be critical for inflammation and cancer progression. This model provides a valuable platform for dissecting ETBF’s colitis-associated cancer-promoting mechanisms, particularly those involving BFT, and for evaluating BFT-targeted therapeutic interventions. Full article

Background: Ulcerative colitis (UC) is a chronic inflammatory condition associated with the colon and rectum, often predisposing individuals to inflammatory bowel disease-related colorectal cancer (IBD-CRC). Current therapeutic options for UC, including corticosteroids and immunosuppressive drugs, pose significant side effects. Punica granatum peel powder (PPPG), a traditional herbal remedy in Ayurveda medicine for colitis, exhibits promising therapeutic effects with a favorable safety profile. Objectives: This study aims to explore the therapeutic potential and mechanism of action of a modified PPPG formulation in UC treatment. Methods: Using NCM460 cells and an acetic acid-induced UC murine model, the efficacy of modified PPPG was evaluated. Results: Therapy with modified PPPG significantly improved UC-associated symptoms, such as improvements in body weight, colon length, and disease activity index, as validated by histological examination. Transcriptomic sequencing identified downregulation of the IL-6/STAT3 signaling pathway and reduced inflammatory markers like p-NF-κB, IL-1β, and NLRP3 on PPPG therapy. Conclusions: These findings suggest that modified PPPG holds promise as a novel therapeutic strategy for UC intervention, targeting key inflammatory pathways implicated in UC pathogenesis and potentially mitigating the risk of IBD-CRC. Full article

The clinicopathologic and molecular features of serrated lesions with dysplasia in inflammatory bowel disease (IBD) remain poorly understood. We examined a total of 2396 patients treated for IBD at the University of Szeged between 2011 and 2023. Among them, 177 (7%) patients were diagnosed with colorectal neoplasia, of which only 11 (6%) had serrated dysplasia (n = 13). Of the 13 lesions, 5 (38%) showed features of sessile serrated lesion (SSL)-like dysplasia; 1 (8%) exhibited characteristics of traditional serrated adenoma (TSA)-like dysplasia; 6 (46%) were classified as serrated dysplasia, not otherwise specified (NOS); and 1 (8%) displayed mixed features of SSL-like and TSA-like dysplasias. At the time of the serrated dysplasia diagnosis, the mean age of the patients was 56 years. Ten (91%) patients had ulcerative colitis, and one (9%) had Crohn’s disease. Pancolitis was observed in seven (64%) patients. The mean duration of IBD at the time of the serrated dysplasia diagnosis was 26 years. Most lesions (n = 9; 69%) were found in the left colon, including SSL-like dysplasia (3/5; 60%) and serrated dysplasia NOS (5/6, 83%). Eleven (85%) lesions had a polypoid endoscopic appearance. The mean size of the serrated dysplasia was 0.8 cm. Most lesions (n = 8; 62%) showed low-grade dysplasia. Serrated dysplasia was often associated with conventional (n = 3; 27%) or nonconventional dysplasia (n = 3; 27%). During the follow-up, 5 (45%) of the 11 patients developed colorectal cancer, including 3 patients with serrated dysplasia NOS, 1 with SSL-like dysplasia, and 1 with TSA-like dysplasia. Whole-exome sequencing revealed that the SSL-like dysplasia harbored mutations in BRAF (p.V600E), MLH1, KRAS, PTEN, POLE, KMT2C, and/or EXT1, whereas the serrated dysplasia NOS showed mutations in TP53, POLG, BRAF (p.G469A), KMT2C, and/or EXT1. One patient with both SSL-like dysplasia and mixed SSL-like/TSA-like dysplasia carried a pathogenic MUTYH (p.R217H) mutation, along with mutations in MADD. Serrated dysplasia was rare in IBD, with a prevalence rate of 6%. The SSL-like dysplasia exhibited distinct clinicopathologic and molecular characteristics compared with its sporadic counterpart. Similarly, serrated dysplasia NOS displayed unique molecular features compared with SSL-like dysplasia and could carry a higher risk of malignancy. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation and debilitating symptoms that considerably impair life quality. UC is particularly prevalent in younger populations, where early diagnosis remains challenging owing to nonspecific symptoms and the potential progression to colitis-associated cancer (CAC). The GSE177044 dataset, consisting of whole blood samples, was analyzed to identify differentially expressed genes, perform gene annotation, analyze key signaling pathways, and detect key hub genes in UC using protein–protein interaction networks. Multiple UC datasets composed of colonic samples were used for validation and examination of methylation and age-related gene expression patterns. Further analyses were performed to explore the association between these key hub genes and colon adenocarcinoma (COAD). We identified four key hub genes—lipocalin-2 (LCN2), matrix metalloproteinase-9 (MMP9), S100 calcium-binding protein A9 (S100A9), and olfactomedin-4 (OLFM4)—significantly up-regulated in UC, with S100A9 showing epigenetic regulation and age-dependent expression patterns. Additionally, S100A9 was strongly associated with poor prognosis in COAD, displaying hypo-methylation and elevated expression, especially in myeloid cell types, and links to altered immune and molecular subtypes. Our findings confirmed the hypo-methylation-driven up-regulation of LCN2, S100A9, and OLFM4 in UC, suggesting their potential as blood-based diagnostic biomarkers. Notably, S100A9 has emerged as a promising biomarker for the early diagnosis of ulcerative colitis, particularly in pediatric and adolescent patients with UC. Moreover, S100A9 holds potential as a precision target to prevent progression from UC to CAC. Full article

Inflammatory bowel disease (IBD)-associated colorectal cancer (CRC) remains a significant clinical challenge due to its link with chronic inflammation and the inherent limitations of current prevention and surveillance strategies. The cGAS-STING pathway has emerged as a key player in the immune regulation of inflammation-driven carcinogenesis, demonstrating both protective and pathogenic roles. This review examines the contrasting roles of the cGAS-STING signaling pathway in intestinal inflammation and colitis-associated cancer (CAC), emphasizing its promise as a target for cancer prevention strategies. Evidence suggests that modulating this pathway could preserve epithelial integrity, limit chronic inflammation, and bolster anti-tumor immunity. Despite advancements in therapies like mesalazine and surveillance colonoscopy programs, gaps in efficacy remain, particularly for Crohn’s disease and high-risk populations. Future research should focus on integrating cGAS-STING-targeted approaches with existing modalities to provide personalized and less invasive strategies for CAC prevention. By harnessing this pathway’s therapeutic potential, a paradigm shift in managing IBD-associated CRC may be achieved, addressing the challenges of long-term disease surveillance and prevention. Full article

Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic condition marked by persistent intestinal inflammation of unknown etiology. Disease onset involves genetic predisposition and environmental factors that disrupt the intestinal immune homeostasis. The intestinal microbiome and immune response play pivotal roles in disease progression. Advances in molecular therapies and early interventions have reduced surgery rates; however, colorectal cancer (CRC) remains a significant concern, driven by chronic inflammation. In UC, the risk of UC-associated neoplasia (UCAN) increases with disease duration, while CD patients face elevated risks of small intestine, anal fistula, and anal canal cancers. Endoscopic surveillance is advised for UCAN, but optimal screening intervals remain undefined, and no established guidelines exist for CD-associated cancers. UCAN morphology often complicates detection due to its flat, inflammation-blended appearance, which differs pathologically from sporadic CRC (sCRC). UCAN is frequently surrounded by dysplasia, with p53 mutations evident at the dysplasia stage. IBD-associated gastrointestinal cancers exemplify inflammation-driven carcinogenesis with distinct molecular mechanisms from the adenoma-carcinoma sequence. This review explores the epidemiology, risk factors, clinical and pathological features, current surveillance practices, and molecular pathways underlying inflammation-associated cancers in IBD. Full article

Introduction: In the general population, right I-sided dysplasia presents a higher risk for colorectal cancer (CRC) and metachronous dysplasia compared to left (L)-sided dysplasia. Given that patients with inflammatory bowel disease (IBD) are at higher risk for dysplasia than the general population, we sought to assess the risk factors as well as the differences in outcomes between patients with R-sided, L-sided, and both R- and L-sided dysplasia. Methods: A retrospective chart review was performed on patients at NYU Langone Health who had evidence of dysplasia on a colonoscopy between 2011 and 2021. Demographics and pertinent medical history were compiled. Cohorts were based on the dysplasia location (R-sided, L-sided, or R- and L-sided) and the IBD-related outcomes were analyzed. Results: A total of 71 patients had colonic dysplasia. The mean age was 54 years old (SD ± 17). The majority were male (72%), white (69%), and non-Hispanic (94%). A total of 76% had ulcerative colitis (UC) and 24% had Crohn’s disease (CD). Of all dysplastic lesions, 57 (80%) patients had unifocal disease and the remainder had multifocal disease. A total of 39 (55%) patients had R-sided dysplasia, 24 (34%) had L-sided dysplasia, and 8 (11%) had both R- and L-sided dysplasia. Patients with UC were more likely to have L-sided dysplasia (92% vs. 8% in CD; p = 0.04). Pseudopolyps were more likely associated with R- and L-sided dysplasia (38% in R- and L-sided dysplasia, 10% in R-sided dysplasia, and 4% in L-sided dysplasia; p = 0.03). Conclusions: Patients with UC had a higher risk for L-sided colonic dysplasia compared to patients with CD; however, there were no differences in the progression of dysplasia between those who had R-sided and those who had L-sided dysplasia. Larger studies are needed to assess the risk factors and outcomes related to the laterality of dysplasia and further validate these findings among patients with IBD. Full article

Background/Objectives: Renal cell cancer is a rare occurrence in patients with ulcerative colitis (UC), with no clearly demonstrated association between UC and an increased risk of renal malignancies. In this article, a case report concerning this relationship is presented. Methods: Our research group presented a case of clear cell renal carcinoma in a 56-year-old male with UC who had previously undergone ileorectal anastomosis and subtotal colectomy. Results: The patient developed a complex renal cyst that progressed to malignancy within one year while on immunosuppressive therapy with infliximab and then filgotinib. Previous ultrasound examinations of the kidney highlighted only simple cysts in the contralateral kidney in previous years. The neoplasm was promptly examined using contrast-enhanced ultrasound, confirming the diagnosis of a Bosniak IV cyst, which was corroborated by a subsequent computed tomography study. Conclusions: The patient underwent a nephrectomy and is currently scheduled for therapy with vedolizumab. Given the increasing use of biologics and small molecules in UC management, periodic ultrasound screening may be a valuable tool for the long-term monitoring of these patients. Full article

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a rising global health issue. Chronic intestinal inflammation is an important risk factor for colorectal cancer (CRC). Despite significant progress in IBD and CRC treatment, numerous patients remain resistant to standard pharmacotherapy or experience severe side effects that prevent them from continuing treatment. There is evidence suggesting that bioactive substances in Lentinula edodes have immunomodulatory and anticancer properties. This fungus is currently classified as a functional food, considering its beneficial effects on human health and special nutritional value. Studies conducted in vitro and in animal models demonstrated that L. edodes bioactive compounds, in particular glucans, have anti-inflammatory and antioxidant effects, induce apoptosis of cancer cells, reduce tumor angiogenesis, restore gut microbiome heterogeneity and improve gut barrier dysfunction. Moreover, clinical trials confirmed that these compounds combined with standard chemotherapy have a significant effect in improving the prognosis of CRC patients. In addition, L. edodes glucans increase microbial diversity and enhance interferon (IFN)-γ production by immune cells. Future studies must be focused on understanding the pathways and mechanisms associated with the observed effects. Moreover, both randomized trials and long-term follow-up studies are needed to confirm their effectiveness in the treatment of IBD and CRC. Full article

Myeloid-derived suppressor cells (MDSCs) regulate immune responses in many pathological conditions, one of which is inflammatory bowel disease (IBD), an incurable chronic disorder of the digestive tract and beyond. The pathophysiology of IBD remains unclear, likely involving aberrant innate and adaptive immunity. Studies have reported altered population of MDSCs in patients with IBD. However, their distribution varies among patients and different preclinical models of IBD. The expansion and activation of MDSCs are likely driven by various stimuli during intestinal inflammation, but the in-depth mechanisms remain poorly understood. The role of MDSCs in the pathogenesis of IBD appears to be paradoxical. In addition to intestinal inflammation, suppressive MDSCs may promote colitis-to-colon cancer transition. In this Review, we summarize recent progresses on the features, activation, and roles of MDSCs in the development of IBD and IBD-associated colon cancer. Full article