Occurrence Of Colitis Research Articles

NVESTIGAÇÃO CLÍNICA DE DOENÇA INFLAMATÓRIA INTESTINAL EM CÃES (DII): ESTUDO DE CASO

Inflammatory Bowel Disease (IBD) in dogs is a chronic condition that affects the gastrointestinal tract, manifesting through symptoms such as diarrhea, vomiting, and weight loss. This case study aims to analyze the occurrence of IBD in a dog, highlighting the difficulties in early diagnosis and appropriate treatment. The medical record of a dog with chronic gastrointestinal symptoms was reviewed, focusing on the tests performed and the treatment administered. The analysis revealed shortcomings in the diagnostic process, including the underutilization of complementary tests, such as endoscopy with biopsy, and the lack of early referral to a veterinary gastroenterology specialist. The study emphasizes the importance of a specific clinical protocol for differential diagnosis and appropriate treatment of IBD.

Investigating the causal relationship between inflammatory bowel disease and simple appendicitis using Mendelian randomization

The relationship between simple appendicitis and inflammatory bowel disease (IBD) is not clear. In this study, we approach the issue from a genetic perspective, using Mendelian randomization (MR) tools to explore the potential causal connection between the two. We used GWAS data from 12,882 IBD patients (21,770 controls), 5956 crohn’s disease (CD) patients (14,927 controls), 6968 ulcerative colitis (UC) patients (20,464 controls), and 4604 simple appendicitis patients (481,880 controls). These statistical data were derived from a large-scale whole-genome association study of individuals with European ancestry. The primary analytical method for inferring the causal relationship between the conditions involved the use of the Inverse Variance Weighting (IVW) method as the main approach for bidirectional MR analysis. The MR analysis results predicted IBD was associated with a lower risk of simple appendicitis (OR: 0.947 (0.911, 0.984), p = 0.005). The results for CD (OR: 0.948 (0.916, 0.981), p = 0.002) and UC (OR: 0.954 (0.917, 0.992), p = 0.020) are consistent with this finding. In the reverse MR analysis, there is no significant association between simple appendicitis and the occurrence of IBD (p > 0.05), and the same holds true for CD and UC (p > 0.05). Our MR study results suggest a potential negative causal effect of IBD on the occurrence of simple appendicitis. Conversely, there does not appear to be a significant causal relationship between simple appendicitis and the risk of developing IBD.

Systemic amyloidosis following inflammatory bowel disease, follicular lymphoma, and diffuse large B-cell lymphoma: a case report

Systemic amyloidosis is a rare disorder characterized by the widespread deposition of misfolded amyloid proteins in several organs, leading to organ failure and potentially death if not promptly recognized. The occurrence of inflammatory bowel disease (IBD), follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL) developing into systemic amyloidosis is uncommon. Here is a case of a 55-year-old Asian woman with a history of IBD, follicular lymphoma, and abdominal DLBCL who developed systemic amyloidosis affecting her gastrointestinal, cardiac, and renal organs. Gastrointestinal symptoms (abdominal pain and melena) initially manifested in this patient with systemic amyloidosis. She underwent treatment with three cycles of rituximab and bendamustine. However, she passed away after 2 months of hospitalization due to multiple organ failure. Hence, physicians must be vigilant in recognizing amyloidosis as a potential complication of lymphoma or other inflammatory diseases, as early recognition can contribute to improved clinical outcomes.

Causality of inflammatory bowel disease and seborrheic keratosis: A bidirectional two-sample Mendelian randomization study.

Previous studies have revealed a potential link between inflammatory bowel disease (IBD) and seborrheic keratosis (SK). However, whether this association is causal or confounded remains unknown. We conducted this two-sample Mendelian randomization (TSMR) analysis to clarify bidirectional causality between IBD, including its two primary conditions Crohn's disease (CD) and ulcerative colitis (UC), and SK. The summary genetic data of IBD, CD, UC and SK were obtained from accessible genome-wide association studies (GWAS). This TSMR study was primarily performed using inverse-variance weighted (IVW) method, complemented by MR-Egger, weighted median (WM), Bayesian weighted MR (BWMR), MR-robust adjusted profile score (MR-RAPS), MR-pleiotropy residual sum and outlier (MR-PRESSO), and radial IVW MR analyses with modified second-order weights (IVW [Mod 2nd]) methods. Assessment of sensitivity and identification of potential outliers were subsequently conducted to aid interpretation of results. The forward MR results showed that IBD [odds ratio (OR)=1.068, 95% confidence interval (CI)=1.010-1.129, p=0.020) and its subtype CD (OR=1.088, 95%CI=1.038-1.139, p<0.001) increased the risk of SK. However, the occurrence of SK could not be affected by UC (OR=1.090, 95%CI=0.977-1.216, p=0.123). In the reverse analysis, no causal relationship between SK and IBD (OR=0.905, 95%CI=0.813-1.008, p=0.069), UC (OR=0.959, 95%CI=0.860-1.068, p=0.443), and CD (OR=0.933, 95%CI=0.846-1.029, p=0.165) was identified. These findings demonstrate that IBD and its subtype CD could increase the incidence of SK in European populations, whereas SK does not affect IBD occurrence.

Study of the relationship between genetic variants of IL-18 and the occurrence of inflammatory bowel disease

BackgroundA member of the Interleukin-1 superfamily of cytokines, interleukin-18 (IL-18) is essential to the etiology and progression of inflammatory bowel disease (IBD), a chronic inflammatory illness that affects the digestive system. This study investigated the possible association between two genetic variations, IL-18 rs187238 and IL-18 rs1946518, and IBD in Iraqi patients.MethodsWe evaluated the association of two SNPs of the IL-18 gene at rs187238 and rs1946518 in 54 IBD patients with 19 Crohn’s disease (CD), 35 ulcerative colitis (UC), and 46 healthy controls using PCR-RFLP and PCR-AS techniques for detecting IL-18 rs187238 and IL-18 rs1946518, respectively, by extracting genomic DNA from blood samples.ResultsOur findings indicated no statistically significant variations between the IL-18 rs187238 genotypes and incidences of CD and UC (P = 0.189 and 0.59, respectively). However, the allele frequency showed a significant difference with CD (P = 0.049) but did not show a significant association with UC (P = 0.887). There was no significant association between the genotype and allele frequency of IL-18 rs1946518C/A and CD risk (P = 0.171 and 0.053, respectively). However, there was a significant association between the genotype and allele frequency of IL-18 rs1946518C/A and the risk of developing UC (P = 0.028 and 0.002, respectively).ConclusionThe study revealed statistically significant distinctions between the genetic and allelic frequencies of IL-18 rs1946518 and the probability of developing UC. Nonetheless, there were no significant distinctions between them and CD. According to the research, there were no major differences between IL-18 rs187238 and the two diseases. The frequency of the C allele is connected to CD.

The causal association between inflammatory bowel disease and breast cancer: a bidirectional two-sample Mendelian randomization study.

Objective: This Mendelian Randomization (MR) study aims to explore the potential bidirectional causal relationship between Inflammatory Bowel Disease (IBD) and Breast Cancer (BC). Materials and Methods: We utilized genetic instruments from the summary statistics of genome-wide association studies (GWAS) on IBD among individuals of European ancestry (12,882 cases and 21,770 controls) to investigate the association with breast cancer (14,910 cases and 17,588 controls) and vice versa. The primary causal estimates were obtained using the Inverse Variance Weighting Method (IVW), and the robustness of the results was evaluated through a series of sensitivity analyses. Results: The study found a positive impact of genetically predicted IBD on breast cancer (OR = 1.047; 95% CI:1.009-1.087; p = 0.014); in the analysis of IBD subtypes, genetically predicted Crohn's Disease (CD) also had a positive effect on breast cancer (OR = 1.044; 95% CI:1.015-1.073; p = 0.002), but genetically predicted Ulcerative Colitis (UC) did not show a significant effect on breast cancer (p > 0.05). The reverse Mendelian Randomization analysis indicated that genetically predicted breast cancer promoted the overall occurrence of IBD (OR = 1.112; 95% CI:1.022-1.211; p = 0.014); however, genetically predicted breast cancer did not show a significant correlation with IBD subtypes (CD and UC) (p > 0.05). Genetic predictions indicate a positive effect of Crohn's Disease (CD) on the risk of Estrogen Receptor-Positive Breast Cancer (ER + BC), with (OR = 1.021; 95% CI:1.002-1.040; p = 0.002). Furthermore, a reverse Mendelian randomization analysis reveals that genetically predicted ER + BC contributes to the increased incidence of ulcerative colitis (UC), as indicated by (OR = 1.098; 95% CI:1.032-1.168; p = 0.003). In contrast, genetically predicted Estrogen Receptor-Negative Breast Cancer (ER-BC) has been shown to promote the overall occurrence of inflammatory bowel disease (IBD), with (OR = 1.153; 95% CI:1.008-1.319; p = 0.037). However, bidirectional two-sample Mendelian randomization analyses between other pairs did not reveal any significant associations (p > 0.05). Conclusion: This study elucidates the bidirectional causal association between breast cancer and inflammatory bowel disease, highlighting the necessity of screening for IBD in breast cancer patients and for breast cancer in IBD patients in clinical settings.

More on the interplay between gut microbiota, autophagy, and inflammatory bowel disease is needed.

The concept of inflammatory bowel disease (IBD), which encompasses Crohn's disease and ulcerative colitis, represents a complex and growing global health concern resulting from a multifactorial etiology. Both dysfunctional autophagy and dysbiosis contribute to IBD, with their combined effects exacerbating the related inflammatory condition. As a result, the existing interconnection between gut microbiota, autophagy, and the host's immune system is a decisive factor in the occurrence of IBD. The factors that influence the gut microbiota and their impact are another important point in this regard. Based on this initial perspective, this manuscript briefly highlighted the intricate interplay between the gut microbiota, autophagy, and IBD pathogenesis. In addition, it also addressed the potential targeting of the microbiota and modulating autophagic pathways for IBD therapy and proposed suggestions for future research within a more specific and expanded context. Further studies are warranted to explore restoring microbial balance and regulating autophagy mechanisms, which may offer new therapeutic avenues for IBD management and to delve into personalized treatment to alleviate the related burden.

The Effect of Protein Nutritional Support on Inflammatory Bowel Disease and Its Potential Mechanisms.

Inflammatory bowel disease (IBD), a complex chronic inflammatory bowel disorder that includes Crohn's disease (CD) and Ulcerative Colitis (UC), has become a globally increasing health concern. Nutrition, as an important factor influencing the occurrence and development of IBD, has attracted more and more attention. As the most important nutrient, protein can not only provide energy and nutrition required by patients, but also help repair damaged intestinal tissue, enhance immunity, and thus alleviate inflammation. Numerous studies have shown that protein nutritional support plays a significant role in the treatment and remission of IBD. This article presents a comprehensive review of the pathogenesis of IBD and analyzes and summarizes the potential mechanisms of protein nutritional support in IBD. Additionally, it provides an overview of the clinical effects of protein nutritional support in IBD and its impact on clinical complications. Research findings reveal that protein nutritional support demonstrates significant benefits in improving clinical symptoms, reducing the risk of complications, and improving quality of life in IBD patients. Therefore, protein nutritional support is expected to provide a new approach for the treatment of IBD.

Effects of proton pump inhibitors on inflammatory bowel disease: An updated review.

Inflammatory bowel disease (IBD) is believed to be caused by various factors, including abnormalities in disease susceptibility genes, environmental factors, immune factors, and intestinal bacteria. Proton pump inhibitors (PPIs) are the primary drugs used to treat acid-related diseases. They are also commonly prescribed to patients with IBD. Recent studies have suggested a potential association between the use of certain medications, such as PPIs, and the occurrence and progression of IBD. In this review, we summarize the potential impact of PPIs on IBD and analyze the underlying mechanisms. Our findings may provide insights for conducting further investigations into the effects of PPIs on IBD and serve as an important reminder for physicians to exercise caution when prescribing PPIs to patients with IBD.

Mortality of Patients With Inflammatory Bowel Disease in the Faroe Islands From 1966-2020.

Increased mortality rates have been found in patients suffering from inflammatory bowel disease (IBD). The Faroe Islands have the highest occurrence of IBD, mainly ulcerative colitis (UC). This study investigated mortality of patients with IBD compared with the general Faroese population. All patients diagnosed with IBD from 1966-2020 were included, as well as population mortality data. All-cause and cause-specific mortality in the IBD cohort was compared with the population by standardized incidence ratios (SIRs). Risk factors for death within the cohort were assessed by hazard ratios (HRs) using Cox regression. Overall mortality was not increased in patients with Crohn's disease (CD; SIR 0.9; 95% confidence interval [CI], 0.56-1.35) or UC (SIR 1.0; 95% CI, 0.83-1.25). However, patients with UC had an elevated risk of dying from digestive diseases (SIR 4.3; 95% CI, 2.16-7.74). Patients with IBD had lower risk of death of cardiovascular diseases compared with the background population (SIR 0.7; 95% CI, 0.50-0.93). Risk factors for mortality included male gender, age at diagnosis, and use of steroids. Protective factors were use of 5-aminosalicylic acid (5-ASA), thiopurines, and biological treatment. No increased risk of all-cause mortality in patients with CD or UC was found in this nationwide study compared with the entire Faroese population over more than 5 decades. The risk of death due to digestive diseases was, however, increased in patients with UC, while mortality risk of cardiovascular diseases was lower in patients with IBD.

Therapeutic Prospects of Mesenchymal Stem Cell and Their Derived Exosomes in the Regulation of the Gut Microbiota in Inflammatory Bowel Disease.

Mesenchymal stem cells (MSCs) have shown great potential in the treatment of several inflammatory diseases due to their immunomodulatory ability, which is mediated by exosomes secreted by MSCs (MSC-Exs). The incidence of inflammatory bowel disease (IBD) is increasing globally, but there is currently no long-term effective treatment. As an emerging therapy, MSC-Exs have proven to be effective in alleviating IBD experimentally, and the specific mechanism continues to be explored. The gut microbiota plays an important role in the occurrence and development of IBD, and MSCs and MSC-Exs can effectively regulate gut microbiota in animal models of IBD, but the mechanism involved and whether the outcome can relieve the characteristic dysbiosis necessary to alleviate IBD still needs to be studied. This review provides current evidence on the effective modulation of the gut microbiota by MSC-Exs, offering a basis for further research on the pathogenic mechanism of IBD and MSC-Ex treatments through the improvement of gut microbiota.

17β-estradiol promotes myeloid-derived suppressor cells functions and alleviates inflammatory bowel disease by activation of Stat3 and NF-κB signalings

Inflammatory bowel disease (IBD) describes a group of clinically common autoimmune diseases characterized by chronic intestinal inflammation, with gender differences in prevalence. Estrogen has been previously shown to exert anti-inflammatory action in IBD development, however, the mechanisms remain obscure. Recent research has revealed that myeloid-derived suppressor cells (MDSCs) play a protective role in IBD pathogenesis. To investigate the molecular mechanisms of estrogen steroid 17β-estradiol (E2) in IBD progression, we established IBD mouse models (DNB-induced) with or without prior ovariectomy (OVX) and E2 implantation. We found that OVX led to worse IBD symptoms and reduced MDSCs frequency, whereas E2 significantly alleviated these effects in vivo. Moreover, in vitro experiments showed that E2 promoted the proliferation and immunosuppressive function of MDSCs through phosphorylation of Stat3 and p65. Mechanistically, E2-mediated Stat3/p65 phosphorylation depends on the interaction between HOTAIR, a long non-coding RNA that are well-known in MDSCs proliferation, and Stat3/p65 respectively. In conclusion, our study revealed that E2 promotes the expansion and immunosuppressive function of MDSCs, and thus diminished the occurrence and development of IBD.

Indole-3-acetic acid alleviates DSS-induced colitis by promoting the production of R-equol from Bifidobacterium pseudolongum

ABSTRACT Background Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis. Method C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, Bifidobacterium pseudolongum, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics. Result In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of Bifidobacterium pseudolongum significantly increased in the IAA treatment group. Bifidobacterium pseudolongum ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice. Conclusion Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from Bifidobacterium pseudolongum, which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.

Innovative probiotic Escherichia coli nissle 1917-derived outer membrane vesicles coupled microspheres demonstrate anti-inflammatory and barrier-enhancing properties in colitis

Occurrence of inflammatory bowel disease (IBD) is increasing worldwide and has become a global health threat. Nonetheless, the effective prevention and available treatment interventions of IBD are limited. Bacterial outer membrane vesicles (OMVs) derived from probiotic bacteria such as Escherichia coli Nissle 1917 (EcN) exhibit promising anti-inflammatory, anti-oxidant, immunomodulatory, and gut microbiota modulatory functions. However, the application of OMVs in vivo encounters potential challenges due to poor tolerance against gastric juice. A delivery system of probiotic-EcN-derived OMVs was established by aldehyde-coupling to silica microspheres (SAP@OMVs) in this study. These SAP@OMVs microspheres were nontoxic to murine macrophage RAW 264.7 and human intestinal epithelial cell lines Caco-2. In the dextran sulfate sodium (DSS)-induced acute colitis models, the application of SAP@OMVs significantly improved mouse survival and alleviated the harmful effects of DSS by maintaining colon length, reducing colon injury, decreasing expression of inflammatory factors such as TNF-α and IL-1β, and increasing expression of the tight junction proteins gene zonula occludens-1 (ZO-1). The SAP@OMVs restored gut microbiota with increasing abundance of the Lactobacillus. In conclusion, the novel vehicle of OMVs demonstrated anti-inflammatory effects, representing a crucial strategy for clinical translation of OMVs as a potential therapeutic intervention for IBD.

Risk of malignancy in a high-incidence population-based cohort of Faroese patients with inflammatory bowel disease from 1960 to 2020 – a Faroese IBD cohort study

Background The association between inflammatory bowel disease (IBD) and malignancy remains disputed despite many observational studies. The Faroese population exhibits the highest occurrence of IBD in the world. This study aimed to investigate the cancer risk in Faroese IBD patients in a nationwide IBD cohort. Methods This study included all IBD patients diagnosed in the Faroe Islands between 1960 and 2020. Clinical demographics and cancer diagnoses were retrieved from patient files and the Faroese cancer registry. Cancer risk in IBD patients was calculated as standardized incidence ratios (SIRs) based on the Faroese background population’s age- and sex-specific cancer incidence rates, retrievable from NORDCAN. Results The cohort consisted of 699 patients with a total follow-up time of 9,629 person-years. Overall, the risk of cancer was not statistically significantly increased compared to the background population. Patients diagnosed with cancer at age 50–59 years had higher overall cancer risk (SIR 1.8; 95% CI, 1.02–2.99) as did UC patients diagnosed with IBD at 50–59 (SIR 2.1; 95% CI, 1.10–3.54). Absolute numbers were small and no estimates for site-specific cancers reached statistical significance, though lung, breast, and cancer of the female reproductive organs were elevated among IBD and UC patients, and colorectal cancer in CD patients. Conclusions This nationwide study found no statistically significantly increased risk of cancer among Faroese patients with CD or UC, except from age 50 to 59 years. While the incidence of IBD is significantly higher in the Faroe Islands than in other countries, risk estimates of cancers are comparable.

THE ROLE OF MICROBIOTA IN INFLAMMATORY BOWEL DISEASES: A LITERATURE REVIEW

The gut microbiome is an ecosystem of the digestive system that synthesizes enzymes and vitamins needed for the proper functioning of the digestive process. In addition, it plays a key function in homeostasis between the digestive and immune systems. Abnormalities in the composition of the gut microbiome have been linked to the occurrence of inflammatory bowel diseases. Numerous reports in the literature suggest that microbes, or substances produced by them, can be a treatment in themselves, or an adjunctive treatment in inflammatory bowel diseases. Methods: In our work we used scientific sources such as publications, guidelines and textbooks. Purposes: In this paper we have compiled information on the mechanism of action of the human gut microbiota. Its influence on the immune system, as well as the mechanism of action of processes occurring in the intestinal wall. In addition, we have compiled information on the relationship between the gut microbiota and inflammatory bowel disease alongside potential treatment and effects of probiotics, prebiotics, antibiotics and fecal microbiota transplantation. Our work focuses mainly on crohn's disease and ulcerative colitis. We have discussed their current treatments and the possibilities and effectiveness of probiotic therapy for both diseases. Conclusion: Intestinal flora disorders are observed both in ulcerative colitis and Crohn's disease. It is believed that it may also be one of the etiopathogenetic factors of these diseases. It has been noted that the use of probiotics in combination with standard treatment promotes remission in ulcerative colitis but has no effect in patients with Crohn's disease.

Familial Mediterranean fever in Armenian children with inflammatory bowel disease.

Inflammatory bowel disease (IBD) and familial Mediterranean fever (FMF) are inflammatory diseases with complex interactions among genetic, immune, and environmental factors. FMF is a monogenic autoinflammatory disease, characterized by recurrent febrile attacks and polyserositis, and is manifested mainly in childhood. FMF is widespread in Armenia. There are reports on the concurrent occurrence of FMF and IBD. MEFV gene mutations may have a disease-modifying effect on IBD. We have investigated the frequency of MEFV mutations and FMF in Armenian children with IBD and their influence on the clinical course. A total of 69 untreated IBD patients under 18 years of age were enrolled: 52.1% (36) had ulcerative colitis (UC), 21.7% (15) had Crohn's disease (CD), and 26.0% (18) had unclassified colitis (IBD-U). The frequency of FMF among them was 36.2% (25/69), and MEFV mutations were identified in 53.6% (37/69). The highest rate of MEFV mutations and FMF was in UC patients (61.1% and 41.6% respectively). In all, 56.7% (21/37) of IBD patients with MEFV mutations had M694V mutated alleles, mainly in compound heterozygous and heterozygous states. There were no associations in the group of IBD patients with coexisting FMF (25), either between any MEFV mutation and type of IBD or coexistence of FMF. Overall, 36.0% (9/25) of them developed VEO IBD and carried mainly the M694V mutation. We concluded that the carrier frequency of MEFV mutations among Armenian pediatric IBD patients was rather high (53.6%), especially for UC. It was suggested that the MEFV gene is not necessarily a susceptibility gene but most likely modifies the course of IBD. MEFV genetic testing was recommended for Armenian pediatric IBD patients, especially for VEO UC and IBD-U, atypical IBD course, or resistance to the conventional treatment. They should also be asked for isolated febrile attacks, recurrent arthritis, and family history, even in the absence of FMF typical symptoms, to rule out FMF and its complications.

WAY-262611 ameliorates the inflammatory bowel disease by activating Wnt/β-catenin pathway.

Inflammatory bowel disease (IBD) is a non-specific and relapsing intestinal inflammation. The injury and repair of intestinal epithelial together determine the occurrence and development of IBD. Wnt/β-catenin pathway is considered as the key role in the proliferation and differentiation of intestinal stem cells which is negative regulated by Dickkiop (DKKs). WAY-262611 is a novel inhibitor of DKK-1, and has demonstrated therapeutic effect on some disease including osteoporosis. Thus, we investigated the effect of WAY-262611 on IBD. Firstly, a mice model of IBD was established by DSS induction, by which the expression of Wnt3a and DKK-1 were detected by immumohistochemical staining to display their correlation. Next, using WAY-262611 the ameliorative effect on IBD was validated by histopathological staining. Using Mode-k cells the experiments in vitro were also conducted, in which the viability and apoptosis were determined. By detecting expression of Wnt3a and DKK-1 and observing nuclear translocation of β-catenin, the activation of Wnt/β-catenin pathway was validated. Finally, the incidence of the orthotopic colorectal cancer was calculated under continuous administration by DSS. Results demonstrated that the expression of Wnt3a is negative correlated with DKK-1. WAY-262611 ameliorated the IBD and reduced apoptosis of Mode-k cells induced by DSS. The protective effect of WAY-262611 on Mode-k cells is mediated by Wnt/β-catenin pathway activation. In addition, WAY-262611 lowered the incidence rate of orthotopic colorectal cancer. All these results concluded that WAY-262611 could mitigate the IBD by activating Wnt/β-catenin pathway in mice.

P1143 Per- and poly-fluoroalkyl substances (PFAS) exposure is associated with later occurrence of inflammatory bowel disease

Abstract Background Environmental chemical exposures are increasingly acknowledged as risk factors for inflammatory bowel disease (IBD). Per- and poly-fluoroalkyl substances (PFAS), a large class of persistent fluorinated organic chemicals, widely used in the modern environment, may be implicated in IBD etiology, but data are conflicting. Methods We investigated the association of PFAS mixture concentrations in pre-diagnostic serum with adult-onset IBD in a pilot study within the pre-clinical Proteomic Evaluation and Discovery in an IBD Cohort of Tri-service Subjects (PREDICTS) study. This is a nested case-control study of military personnel with Crohn’s disease (CD), ulcerative colitis (UC), and age-, sex-, and race-matched healthy controls with serum samples obtained at four-time points 1-10 years prior to IBD diagnosis. Using untargeted liquid-chromatography high-resolution mass spectrometry analytical approach, we conducted an untargeted metabolomic analysis and semiquantitative measurement of fluorinated compounds, including legacy PFAS and emerging PFAS chemicals. We used weighted quantile sum regression models adjusted for confounders to study the association of PFAS as a mixture with the odds of CD and UC at each time point. Results Our study sample included individuals with CD, UC, and matched healthy controls (n=25, each group, 4 samples per individual). Baseline characteristics were similar across cases and controls. We identified nine well known PFAS compounds and 27 other known fluorinated compounds. The chemical mixture of fluorinated compounds, including the known PFAS, in the serum samples within one year of diagnosis was associated with higher odds of CD and UC [odds ratio (OR) 2.13, 95% CI 1.33, 3.41, and 1.76, 95% CI 1.15, 2.68, respectively] per one unit increase in decile. These associations remained consistent for the PFAS mixture measured in serum at all four time points up to 10 years prior to diagnosis for both CD and UC (Figure). Major contributors to the overall mixture indices included legacy PFAS, as well as emerging PFAS chemicals. Conclusion We observed a substantial increase in the odds of CD and UC among individuals with higher serum PFAS mixture levels up to 10 years prior to diagnosis. Studies to understand underlying mechanisms are ongoing.

P1172 Epidemiology and initial presentation of newly diagnosed inflammatory bowel diseases in a Danish population-based inception cohort – results from the IBD Prognosis Study

Abstract Background It is unclear whether the incidence of inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), continues to increase. In this study, we aimed to investigate the occurrence and initial disease presentation of IBD in a population-based setting. In addition, we aimed to identify predictors of an early severe disease presentation. Methods The study was conducted as part of IBD Prognosis Study, an ongoing Danish prospective population-based inception cohort study that includes incident patients with IBD according to the Copenhagen Diagnostic Criteria since May 2021, covering the catchment areas of approximately 20% of the Danish population (1.1 million). In this analysis, cutoff for data analysis was in May 2023. Crude incidence rates and European Standard Population (ESP)-adjusted rates were calculated. A multivariable logistical regression model was constructed to identify predictors of a severe disease presentation, defined as the composite need for systemic steroids, immunomodulators, biologics, or IBD-related surgery within three months of disease. Results In total, 554 patients (UC: 344, CD: 210) fulfilled the inclusion criteria, resulting in the following crude incidence rates per 100,000 person-years: IBD 23.4 (95% CI 21.5-25.4), UC 14.0 (12.6-15.6), and CD 8.6 (7.4-9.8). ESP-adjusted rates were: IBD 20.4 (18.2-22.9), UC 11.8 (10.2-13.0), and CD 7.9 (6.5-9.9) (Figure 1). Among patients with UC, 81 (26.3%) and 95 (30.8%) had left-sided or extensive colitis at disease onset, respectively, while 61 (30.3%) and 62 (30.8%) patients with CD had ileal or ileocolonic disease. Stricturing or penetrating CD behaviour was observed in 24 (11.9%) and 11 (5.5%) patients, respectively. A high proportion of patients needed hospitalization (CD: 68 (33.8%), UC: 60 (19.5%), p=0.001) and IBD-related surgery (CD: 21 (10.4%), UC: 10 (3.2%), p=0.004) at the time of diagnosis. In multivariable analysis, a severe disease presentation of UC at the time of diagnosis was associated with left-sided or extensive disease distribution, thrombocytosis, and increased levels of C-reactive protein (CRP) (Table 1). In patients with CD, stricturing, or perianal disease, as well as anemia, levels of albumin, CRP, and calprotectin were predictive of this endpoint (Table 1). Conclusion The incidence of UC and CD in Denmark appears stable compared to historical data from the previous decades.1 The study identified clinical predictors of a severe disease presentation from the time of diagnosis, emphasizing the critical need for early risk stratification and intervention strategies. Reference: 1 Dorn-Rasmussen M et al., J Crohns Colitis. doi: 10.1093/ecco-jcc/jjac138.