Search Results (172)

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/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

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

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

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

Blastocystis spp. has been linked to gastrointestinal symptoms, yet its pathogenicity remains uncertain. In addition, the roles of virulence factors, pathogenic potential, and host-specific traits associated with symptomatic infections are still not well understood. The growing number of immunocompromised patients has contributed to an increasing prevalence of Blastocystis spp. infections, which may be implicated in the development of various inflammatory diseases, including irritable bowel syndrome (IBS), colorectal cancer, and autoimmune disorders such as Hashimoto’s disease and ulcerative colitis. However, the presence of nonspecific symptoms often complicates diagnosis. This study aimed to present current data on the impact of Blastocystis spp. on the development and progression of gastrointestinal and autoimmune diseases, as well as to explore potential treatment options for Blastocystis spp. infections. A literature review was conducted to analyze the role of Blastocystis spp. in the pathogenesis of specific diseases and to investigate potential mechanisms of its interaction with the host organism. Advances in diagnostic techniques, particularly PCR, allow not only for the detection of Blastocystis spp. but also for the identification of specific subtypes, improving treatment precision. Beyond conventional therapies like metronidazole, there is a growing emphasis on alternative treatments, including the use of medicinal plants and probiotics. Full article

Background: The perspective of inflammatory bowel disease (IBD) has changed radically since the first decade of the 21st century, and the formerly monolithic components of IBD, ulcerative colitis (UC), and Crohn’s disease (CD) have undergone a fundamental convergence, with realization that there is likely an element of shared pathogenesis. The ground shift began with genomic revelation but with the current emergence of the innate immune system (InImS) as a key player, allowing for improved understanding of the associations between the immune underpinnings of IBD. Methods: Using unique ferritin/fecal p87 (FERAD) or using colonoscopic effluent as denominator (FEREFF) and other ratios to test this hypothesis, we prospectively enrolled 2185 patients with increased risk of colorectal cancer, of whom 31 had UC and 18 CD, with 2136 controls and brought to bear in a convenient measure for the InImS, the FERAD ratio. The FERAD, FEREFF, and NLR ratios have been shown to be effective measures of the InImS in COVID-19 and various cancers. p87 is expressed in gut Paneth cells known to modulate the microbiome by secretion of alpha-defensins, a natural antibiotic. Other related parameters were also evaluated. Results: There was no significant difference between the FERAD ratio in UC and CD. However, differences between IBD entities and controls were substantial. Conclusions: InImS settings in IBD are similar between CD and UC. p87 tissue immunohistochemistry (IHC) is also shared. Other InImS markers, such as the absolute neutrophil/lymphocyte ratio, are also confluent between the two IBD forms. Full article

Patients with long-standing inflammatory bowel disease (IBD) involving the colon are at higher risk of developing colorectal dysplastic or neoplastic lesions. While from sporadic colorectal cancer follows an “adenoma-carcinoma” sequence, IBD colitis-associated carcinogenesis is mainly related to an “inflammation-dysplasia-carcinoma” sequence. Currently, specific endoscopic surveillance strategies involving dye spray and virtual chromoendoscopy have been standardized, aiming for early CRC diagnosis. When detected, colitis-associated dysplasia should be classified according to standard classification, thus allowing for better treatment. Indeed, most IBD-associated dysplastic lesions can be treated with endoscopic resection, even though available procedures are usually more challenging than those in the general population. The higher frequency of severe submucosal fibrosis and the difficulty in the definition of lesions’ margins account for this issue. Current endoscopic resection techniques include polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Recent evidence suggests the relevance of en bloc resection, as this may be associated with lower rates of recurrence. Therefore, particularly for larger (>20 mm) lesions, ESD should be preferred, even though it is considered the most difficult technique due to frequent severe submucosal fibrosis. Considering the growing number of new endoscopic resective techniques, including underwater EMR or ESD, which in the general population have been suggested to lower procedure-related risks and may also allow a larger spread of advanced endoscopic resection in IBD. However, additional data are needed to assess the medium- and long-term efficacy of endoscopic resection of visible dysplasia in IBD patients, which are burdened by a high risk of local and, more importantly, metachronous recurrence. Full article

Colorectal cancer (CRC) is one of the most prevalent causes of cancer-related fatalities globally, and its development is closely associated with dietary and microbial factors. The aim of this study was to investigate the potential of ganjang, a traditional fermented soy sauce, in alleviating colitis-associated colorectal cancer (CAC) in a mouse model induced by azoxymethane/dextran sulfate sodium (AOM/DSS). The bacterial composition of ganjang samples from different regions primarily included Lactobacillus spp. and Bacillus spp. Administration of ganjang to AOM/DSS-induced mice significantly improved CAC-related symptoms, including increased body weight, restored colon length, and reduced spleen size. Additionally, ganjang administration led to a decrease in tumor size and number, the modulation of apoptotic and proliferative markers, decreased inflammatory cytokine levels, and the restoration of the intestinal epithelial barrier. Furthermore, ganjang samples altered the gut microbiota composition by increasing the relative abundance of Lactobacillus spp. These findings suggest that ganjang has potential as a functional food for CRC prevention or mitigation, primarily through the modulation of CAC symptoms, tumor growth, inflammatory responses, intestinal epithelial barrier integrity, and gut microbiota composition. Full article

Inflammatory bowel diseases have long been recognized as entities with a higher risk of colorectal cancer. An increasing amount of information has been published regarding ulcerative colitis-associated colorectal cancer and its unique mechanisms in recent decades, as ulcerative colitis constitutes a chronic process characterized by cycles of activity and remission of unpredictable durations and intensities; cumulative genomic alterations occur during active disease and mucosal healing, resulting in a special sequence of events different to the events associated with sporadic colorectal cancer. The recognition of the core differences between sporadic colorectal cancer and colitis-associated cancer is of great importance to understand and guide the directions in which new research could be performed, and how it could be applied to current clinical scenarios. A DSS/AOM murine model has allowed for a better understanding of the pathogenic mechanisms in colitis-associated cancer, as it is currently the closest model to this unique scenario. In this review, we provide a summary of the main molecular mechanisms and the clinical aspects of colitis-associated cancer in ulcerative colitis. Full article