Risk Of Inflammatory Bowel Disease Research Articles

Inflammatory Bowel Disease and Risk of Global Cardiovascular Diseases and Type 2 Diabetes.

Inflammatory bowel disease (IBD) was associated with elevated risk of cardiometabolic diseases in observational studies. We aimed to evaluate the observational and genetic associations of Crohn's disease (CD) and ulcerative colitis (UC) with multiple cardiometabolic outcomes. Our phenotypic and genetic association analyses included more than 400 000 participants who were free of major cardiovascular disease and diabetes at recruitment (2006-2010) and were followed up until December 2019 based on the UK Biobank. For the Mendelian randomization (MR) analyses, 415 and 273 single nucleotide polymorphisms associated with CD and UC, respectively, were selected as genetic instruments. Summary-level data on individual cardiometabolic outcomes were obtained from 4 different genome-wide association studies with a total of 2 248 842 participants. In the multivariable-adjusted observational analyses, CD was associated with higher risks of heart failure (hazard ratio [HR], 1.72; 95% confidence interval, 1.22-2.42) and type 2 diabetes (HR, 2.11; 95% confidence interval, 1.67-2.67) but not with myocardial infarction or ischemic stroke. UC was related to increased risks of all the assessed cardiometabolic diseases (HRs ranged from 1.29 for myocardial infarction to 1.76 for type 2 diabetes). Conversely, neither the genetic risk score for CD nor that for UC was associated with higher risk of developing cardiometabolic diseases. In 2-sample MR analyses, genetically determined CD and UC were not associated with any of the assessed cardiometabolic diseases (all P values >.05). Despite confirming the observational associations, our study does not support a causal association between IBD and elevated risk of cardiometabolic diseases.

A meta-analysis of the risk of osteoporotic fractures in inflammatory bowel disease.

There are a variety of perspectives on the risk of osteoporotic fractures in inflammatory bowel disease (IBD), and few thorough assessments that are pertinent. We conducted a meta-analysis to assess the risk of osteoporotic fractures in IBD. A systematic literature search up to September 2022 was performed, and 1,158,982 subjects participated in the baseline trials of the selected studies. A total of 261,829 patients had IBD, while 897,153 were controls. Odds ratio (OR) and mean difference (MD) with 95% confidence intervals (95% CIs) were calculated to measure the risk of osteoporotic fractures in IBD patients using contentious and dichotomous approaches with a random or fixed influence model. The presence of IBD resulted in significantly higher frequency of osteoporotic fractures (OR: 1.42, 95% CI: 1.21-1.66, p < 0.001) compared to controls. Nevertheless, no significant differences in terms of osteoporotic fractures were found between ulcerative colitis (OR: 2.79, 95% CI: 0.88-8.87, p = 0.08) and Crohn's disease (OR: 1.84, 95% CI: 0.81-4.18, p = 0.14) compared to controls. This study found a strong correlation between the risk of osteoporotic fractures and inflammatory bowel disease. The small number of studies in certain comparisons requires care when analyzing the results.

The chromatin and single-cell transcriptional landscapes of CD4 T cells in inflammatory bowel disease link risk loci with a proinflammatory Th17 cell population.

The imbalance between Th17 and regulatory T cells in inflammatory bowel diseases (IBD) promotes intestinal epithelial cell damage. In this scenario, T helper cell lineage commitment is accompanied by dynamic changes to the chromatin that facilitate or repress gene expression. Here, we characterized the chromatin landscape and heterogeneity of intestinal and peripheral CD4 T cellsfrom IBD patients using in house ATAC-Seq and single cell RNA-Seq libraries. We show that chromatin accessibility profiles of CD4 T cells from inflamed intestinal biopsies relate to genes associated with a network of inflammatory processes. After integrating the chromatin profiles of tissue-derived CD4 T cells and in-vitro polarized CD4 T cell subpopulations, we found that the chromatin accessibility changes of CD4 T cells were associated with a higher predominance of pathogenic Th17 cells (pTh17 cells) in inflamed biopsies. In addition, IBD risk loci in CD4 T cells were colocalized with accessible chromatin changes near pTh17-related genes, as shown in intronic STAT3 and IL23R regions enriched in areas of active intestinal inflammation. Moreover, single cell RNA-Seq analysis revealed a population of pTh17 cells that co-expresses Th1 and cytotoxic transcriptional programs associated with IBD severity. Altogether, we show that cytotoxic pTh17 cells were specifically associated with IBD genetic variants and linked to intestinal inflammation of IBD patients.

Association between the use of lipid-lowering drugs and the risk of inflammatory bowel disease.

Observational studies have suggested an association between lipid-lowering drugs and inflammatory bowel disease (IBD) risk. This study aimed to assess the causal influence of lipid-lowering agents on IBD risk using Mendelian randomization analysis. In a population of 173,082 individuals of European ancestry, 55 single-nucleotide polymorphisms were identified as instrumental variables for 6 lipid-lowering drug targets (HMGCR, NPC1LC, PCSK9, LDLR, CETP and APOB). Summary statistics for the genome-wide association study of IBD, ulcerative colitis (UC) and Crohn's disease (CD) were obtained from the FinnGen consortium, Program in Complex Trait Genomics and UK Biobank. Inverse-variance weighted was employed as the primary MR method, and odds ratios (ORs) with 95% confidence intervals were reported as the results. Sensitivity analyses using conventional MR methods were conducted to assess result robustness. Gene-proxied inhibition of Niemann-Pick C1-like 1 (NPC1L1) was associated with an increased IBD risk (OR [95% CI]: 2.31 [1.38, 3.85]; p = .001), particularly in UC (OR [95% CI]: 2.40 [1.21, 4.74], p = .012), but not in CD. This finding was replicated in the validation cohort. Additionally, gene-proxied inhibition of low-density lipoprotein receptor was associated with reduced IBD (OR [95% CI]: .72 [.60, .87], p < .001) and UC risk (OR [95% CI]: .74 [.59, .92], p = .006), although this result was not replicated in the validation cohort. Other drug targets did not show significant associations with IBD, UC or CD risk. Inhibition of the lipid-lowering drug-target NPC1L1 leads to an increased IBD risk, mainly in the UC population.

Despite Increased Disease Activity, Women who Attended a Dedicated Inflammatory Bowel Disease and Pregnancy Clinic Had Infants With Higher Apgar Scores: A Population-Based Study.

Attendance at a subspecialty pregnancy clinic for women with inflammatory bowel disease (IBD) improves disease-specific pregnancy knowledge. We examined the impact of attendance at a dedicated IBD-pregnancy clinic on IBD and perinatal outcomes. Using linked administrative databases in Alberta, Canada (2012-2019), we identified 1061 pregnant women with IBD who delivered singleton liveborn infants in-hospital who did (n = 314) and did not attend (n = 747) the clinic. Propensity score weighted multivariable log-binomial and multinomial logistic regression models were used to determine the risk of IBD and perinatal outcomes. The median number of clinic visits was 3 (Q1-Q3, 3-5), with 34.7% completing a preconception consultation. A greater proportion of women who attended lived near the clinic, were nulliparous, had a disease flare prior to pregnancy, and were on maintenance IBD medication (P < .05). Women who attended had increased risks of a disease flare during pregnancy (adjusted risk ratio [aRR], 2.02; 95% CI, 1.45-2.82), an IBD-related emergency department visit during pregnancy (aRR, 2.66; 95% CI, 1.92-3.68), and cesarean delivery (aRR, 1.78; 95% CI, 1.23-2.57). Despite this, clinic attendees had a decreased risk of delivering an infant with a low Apgar score at 1 minute (risk ratio [RR], 0.49; 95% CI, 0.32-0.76) and 5 minutes (RR, 0.32; 95% CI, 0.12-0.87). Women who attended a dedicated IBD-pregnancy clinic were more likely to have a disease flare prior to pregnancy, reflecting a more severe disease phenotype, but had similar perinatal outcomes and infants with better Apgar scores at birth. Our study suggests the value of these subspecialty clinics in providing enhanced IBD-specific prenatal care.

Polymorphisms indicating risk of inflammatory bowel disease or antigenicity to anti-TNF drugs as biomarkers of response in children

Few genetic polymorphisms predict early response to anti-TNF drugs in inflammatory bowel disease (IBD), and even fewer have been identified in the pediatric population. However, it would be of considerable clinical interest to identify and validate genetic biomarkers of long-term response. Therefore, the aim of the study was to analyze the usefulness of biomarkers of response to anti-TNFs in pediatric IBD (pIBD) as long-term biomarkers and to find differences by type of IBD and type of anti-TNF drug. The study population comprised 340 children diagnosed with IBD who were treated with infliximab or adalimumab. Genotyping of 9 selected SNPs for their association with early response and/or immunogenicity to anti-TNFs was performed using real-time PCR. Variants C rs10508884 (CXCL12), A rs2241880 (ATG16L1), and T rs6100556 (PHACTR3) (p value 0.049; p value 0.03; p value 0.031) were associated with worse long-term response to anti-TNFs in pIBD. DNA variants specific to disease type and anti-TNF type were identified in the pediatric population. Genotyping of these genetic variants before initiation of anti-TNFs would enable, if validated in a prospective cohort, the identification of pediatric patients who are long-term responders to this therapy.

Higher dietary fibre intake is associated with lower risk of inflammatory bowel disease: prospective cohort study.

Limited prospective studies that have examined the association of dietary fibre with IBD have provided inconsistent evidence. To examine any associations between dietary fibre intake and subsequent incidence of IBD, Crohn's disease (CD) and ulcerative colitis (UC) METHODS: We conducted a prospective cohort study of 470,669 participants from the UK Biobank and estimated dietary fibre intake from a valid food frequency questionnaire at baseline. Incident IBD was ascertained from primary care data and inpatient data. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between dietary fibre intake and the risk of IBD, CD and UC. During an average follow-up of 12.1 years, we ascertained 1473 incident IBD cases, including 543 cases of CD and 939 cases of UC. Comparing the lowest quintiles, an inverse association was observed between dietary fibre intake and risk of IBD (HR 0.74, 95% CI 0.58-0.93, p = 0.011) and CD (HR 0.48, 95% CI 0.32-0.72, p < 0.001), but not UC (HR 0.92, 95% CI 0.69-1.24, p = 0.595). For specified sources, dietary fibre intake from fruit and bread decreased the risk of CD, while dietary fibre intake from cereal decreased the risk of UC. Higher consumption of dietary fibre was associated with a lower risk of IBD and CD, but not UC. Our findings support current recommendations to increase the intake of dietary fibre.

Inflammatory Bowel Disease Is not Linked to a Higher Rate of Adverse Events in Colonoscopy-a Nationwide Population-based Study in Sweden.

Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study. Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation. Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation. Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.

The Association between Total Protein, Animal Protein, and Animal Protein Sources with Risk of Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Cohort Studies.

We aimed to conduct this dose-dependent meta-analysis to examine the relation between total protein, animal protein, and its sources with inflammatory bowel disease (IBD). We searched databases, comprising PubMed/Medline, Web of Science (ISI), Embase, and Google Scholar, for the published studies up to 28 March 2023. Prospective cohort study designs that investigated associations between dietary intake of various animal protein sources and with risk of IBD in the general population were identified. Eleven prospective cohort studies with 4,302,554 participants and 8067 cases were considered eligible. Findings indicated that higher intake of dairy was significantly associated with a lower risk of IBD (relative risk [RR]: 0.81; 95% confidence interval [CI]: 0.72, 0.90), Crohn disease (RR: 0.69; 95% CI: 0.56, 0.86), and ulcerative colitis (RR: 0.84; 95% CI: 0.75, 0.94). There was no association between different sources of animal protein and the risk of IBD. The dose-response analysis suggested that each 100 g/d increment in dietary total meat consumption was associated with a 38% greater risk of IBD. Moreover, a positive linear association was found between total meat intake and risk of IBD (Pnonlinearity = 0.522, Pdose-response = 0.005). Overall, among the dietary sources of protein, the risk of IBD increased only with increasing total meat intake, and the consumption of protein from dairy products was found to be a protective factor against the IBD risk. This trial was registered at PROSPERO as CRD42023397719.

Evaluation of the effectiveness of telemedical technologies in patients with digestive diseases

BACKGROUND: The use of telemedical technologies (TMT) is widespread in providing care to patients of various profiles. However, TMTs are hardly ever used in gastroenterology, despite the extensive digitalization of healthcare. Potential sites for the use of TMTs among gastroenterological patients were assessed.&#x0D; AIM: The study aimed to assess the effectiveness and benefits of TMTs in patients with digestive diseases.&#x0D; &#x0D; Patients with colorectal cancer (CRC): Screening and postoperative management. The TMT intervention increased the number of patients screened for CRC compared to standard face-to-face counseling. In addition, the quality of preparation for colonoscopy was higher in patients who interacted with the physician via TMTs compared to the control group. Most studies reported positive effects of TMTs on quality of life and physical activity in patients with CRC. However, the study by K. Beaver et al. showed that the incidence of CRC recurrence did not differ in the TMT and face-to-face groups.&#x0D; Patients with nonalcoholic fatty liver disease (NAFLD): Correction of lifestyle. When assessing the use of TMTs among NAFLD patients, a significant decrease in alanine aminotransferase and aspartate aminotransferase activity was found compared to that in face-to-face management. The results of the body mass index reduction are contradictory. The most pronounced tendency towards weight loss was observed with the telemedical follow-up of patients over a 6-month period.&#x0D; Patients with irritable bowel syndrome (IBS): Treatment and monitoring of symptoms. Two directions are distinguished in the treatment of IBS by ТМТs. The first is cognitive behavioral therapy (CBT). H. Everitt et al. showed clinically significant improvement in 72.8% of cases after 12 months of web-based CBT. The advantages of using telemedicine in the delivery of CBT include the geographical independence of the physician and the patient, personalization of treatment, and the possibility of ongoing support for the patient and his or her family. The second direction is the use of special diets, such as low-fermentable nutrient diets (FODMAP). Patients following the FODMAP diet supervised by the mobile app reduced symptom severity (odds ratio 55; 95% confidence interval 1198, p=0.01). Special mobile apps (IBS Constant Care) were used to monitor the condition of patients with IBS, which analyze input data and assess severity, providing information to both the patient and the physician.&#x0D; Patients with inflammatory bowel disease (IBD): Patient training and telemonitoring. The study by L. Pang et al. proved that the patients quality of life in the telemedicine intervention group was significantly higher (p=0.03). Another advantage of using TMTs is the provision of access to educational materials about IBD and the possibility of remote contact with the treating physician. The patients ability to obtain necessary information reduces the need for unplanned visits to medical facilities, thus reducing the cost of organizing medical care for patients with IBD. The degree of IBD activity and risk of recurrence and adherence to therapy did not differ significantly between the telemedicine intervention group and the standard face-to-face follow-up group.&#x0D; &#x0D; METHODS: A literature search relevant to the review was conducted in the PubMed database. The studies taken for assessment were those on the use of TMTs among patients with IBD, IBS, NAFLD, and CRC. TMTs were used to access educational information and dietary recommendations, provide information on lifestyle adjustments and physical activity, remind patients to take medicines, consult with physicians, and assess disease activity by completing online questionnaires. The various studies used text messaging, e-mail, mobile apps, websites, and videoconferencing apps as a means of communication.&#x0D; RESULTS: The use of telemedicine in the management of patients with digestive diseases showed high efficiency. TMTs contribute to:&#x0D; &#x0D; Improved quality of life in patients with digestive diseases.&#x0D; Increasing physical activity of patients with CRC and NAFLD.&#x0D; Improved quality of CRC screening.&#x0D; Maintaining remission of IBD and CRC as effectively as face-to-face monitoring.&#x0D; &#x0D; Moreover, the use of TMTs allows personalized treatment, ensures the ongoing support of the patient and his or her family by the medical staff, and provides patients with access to quality educational materials about the disease.&#x0D; CONCLUSIONS: Thus, the use of TMTs is promising in the treatment of digestive diseases and requires wider introduction into practice.

Telemedical follow-up in patients with inflammatory bowel diseases

Inflammatory bowel diseases (IBDs) represent a group of nosologies including Crohns disease and ulcerative colitis. These diseases lead both to the deterioration of the patients physical condition and to a pronounced decrease in the quality of life. Currently, healthcare costs of managing patients with IBDs are steadily increasing and are commonly associated with the need for examinations and therapy with expensive drugs and unplanned expenses of healthcare resources for unscheduled consultations, emergency hospitalizations, and surgical interventions. Deterioration of patients condition may be associated with self-cancellation of therapy after normalization of the state of health. The use of telemedical technologies (TMTs) is promising for maintaining remission of IBDs, improving adherence to therapy, and reducing the frequency of unscheduled visits to the clinic and the cost of treating IBD complications (including surgery). The efficiency and benefits of TMTs in patients with IBDs were assessed in comparison with standard face-to-face follow-up. A literature search relevant to the review was conducted in the PubMed database. Papers were selected that assessed the efficiency of telemedical interventions among patients with IBDs as compared to the standard face-to-face follow-up group. The evaluation criteria included the degree of the disease activity, risks of IBD recurrence, quality of life of patients, adherence to therapy, healthcare costs, and frequency of visits to healthcare facilities. Telemedical interventions were conducted using the Internet, mobile applications, various telemedical platforms, SMS messages, and phone calls. The telemedical follow-up groups received access to educational materials and online consultations with a specialist upon request and completed questionnaires to assess disease activity, adherence to therapy, and quality of life. The degree of IBD activity and risk of recurrence and the level of adherence to therapy did not differ significantly between the telemedical intervention and standard face-to-face follow-up groups. The study by L. Pang et al. showed that the patients quality of life in the group of telemedical intervention was significantly higher (p=0.03) [8]. Another advantage of using TMTs is the provision of access to educational materials about IBDs and the possibility of remote contact with the treating physician. The patients ability to obtain necessary information reduces the need for unplanned visits to medical facilities and the cost of organizing medical care for patients with IBDs. The use of TMTs allows to monitor IBD activity as effectively as face-to-face follow-up, improve the patients quality of life with IBDs, and reduce costs for organizing care for patients with these diseases by decreasing the frequency of unscheduled visits to the doctor and conducting unnecessary additional examinations.

The Relationship Between Rosacea and Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

Rosacea and inflammatory bowel disease (IBD) are chronic inflammatory disorders of the skin and the gut, which are interfaces between the environment and the human body. Although growing evidence has implicated a possible link between rosacea and IBD, it remains unclear whether IBD increases the risk of rosacea and vice versa. Therefore, we investigated the association between rosacea and IBD in this study. We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Eight eligible studies were included in this meta-analysis. Overall, the prevalence of rosacea was higher in the IBD group than in the control group, with a pooled odds ratio (OR) of 1.86 (95% confidence interval [CI](1), 1.52-2.26). Both the Crohn's disease and the ulcerative colitis groups had higher prevalences of rosacea than the control group, with ORs of 1.74 (95% CI 1.34-2.28) and 2.00 (95% CI 1.63-2.45), respectively. Compared with those in the control group, the risks of IBD, Crohn's disease, and ulcerative colitis were significantly higher in the rosacea group, with incidence rate ratios of 1.37 (95% CI 1.22-1.53), 1.60 (95% CI 1.33-1.92), and 1.26 (95% CI 1.09-1.45), respectively. Our meta-analysis suggests that IBD is bidirectionally associated with rosacea. Future interdisciplinary studies are needed to better understand the mechanism of interaction between rosacea and IBD .

Inflammatory bowel disease and prostate cancer risk: a two-sample Mendelian randomization analysis.

Previous epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis. We performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Genetically determined IBD did not have a causal effect on PCa (IVW P > 0.05). Additionally, there was no causal effect of Crohn's disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P > 0.05). Results of complementary methods were consistent with those of the IVW method. This study does not support a causal association of IBD on PCa, which is in contrast to most observational studies.

Safety of IL-23 p19 Inhibitors for the Treatment of Patients With Moderate-to-Severe Plaque Psoriasis: A Narrative Review.

The approved biologics targeting interleukin (IL)-23 p19 for the treatment of moderate-to-severe plaque psoriasis, including guselkumab, tildrakizumab, and risankizumab, have generally favorable safety profiles. The aim of the current review is to describe in detail the safety of these selective inhibitors. A literature search was performed using PubMed from inception to 1 November 2022, to identify clinical trials and real-world evidence publications using the keywords "guselkumab," "tildrakizumab," and "risankizumab." Overall, the most common adverse events (AEs) associated with IL-23 p19 inhibitors in clinical trials were nasopharyngitis, headache, and upper respiratory tract infections. Rates of serious AEs and AEs of interest, including serious infections, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, major adverse cardiovascular events, and serious hypersensitivity reactions, were not increased with long-term use in clinical trials. Selectively targeting IL-23 p19 was also not associated with elevated risk of opportunistic infections, tuberculosis reactivation, oral candidiasis, or inflammatory bowel disease. Results from real-world studies were similar, supporting the safe long-term use of these biologics in a wider population of patients with psoriasis, including older patients, patients for whom multiple biologics failed, and those with comorbidities such as obesity, metabolic syndrome, cardiovascular disease, dyslipidemia, diabetes, hypertension, and psoriatic arthritis. This review is limited by the lack of direct comparisons among therapeutic agents due to differences among study designs and safety data reporting methods. In conclusion, the favorable safety profiles of IL-23 p19 inhibitors support their long-term use in the management of patients with moderate-to-severe psoriasis.

Association of Depression With Incident Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

Individuals with a history of depression/depressive symptoms are suspected to be at increased risk of incident inflammatory bowel diseases (IBDs). We systematically searched MEDLINE/PubMed, Embase, and Scopus databases for longitudinal studies examining the association between depression/depressive symptoms and subsequent new-onset IBD (ie, Crohn's disease and ulcerative colitis). We included studies in which the exposure was a confirmed diagnosis of depression/depressive symptoms measured through a validated scale. To limit concerns of diagnostic bias and reverse causality, and support temporality between exposure and outcomes, we synthesized estimates corresponding to the longest time lag reported. Two authors extracted study data independently and assessed each study's risk of bias. Maximally adjusted relative risk (RR) estimates were synthesized using random- and fixed-effects models. Of 5307 records, 13 studies (8 cohort and 5 nested case-control studies; 9 million individuals) fulfilled the eligibility criteria. Depression was significantly associated with incident Crohn's disease (RRrandom, 1.17; 95% confidence interval, 1.02-1.34; 7 studies, 17 676 cases) and ulcerative colitis (RRrandom, 1.21; 95% confidence interval, 1.10-1.33; 6 studies, 28 165 cases). The primary studies considered pertinent confounders. Several years, on average, separated exposure and outcomes. No evidence of important heterogeneity or publication bias was found. Summary estimates were at low risk of bias, and results were confirmed in multiple sensitivity analyses. No firm conclusions could be drawn regarding a dilution of the association over time. Individuals with a history of depression may show small-to-moderate increased risk of IBD even when depression is diagnosed several years before new-onset IBD. Further epidemiological and mechanistic studies should clarify whether these associations are causal.

Zearalenone Exposure Disrupts STAT-ISG15 in Rat Colon: A Potential Linkage between Zearalenone and Inflammatory Bowel Disease.

Zearalenone (ZEN), a prevalent mycotoxin contaminating food and known for its intestinal toxicity, has been suggested as a potential risk factor for inflammatory bowel disease (IBD), although the exact relationship between ZEN exposure and IBD remains unclear. In this study, we established a rat model of colon toxicity induced by ZEN exposure to investigate the key targets of ZEN-induced colon toxicity and explore the underlying connection between ZEN exposure and IBD. Histological staining of the rat colon revealed significant pathological changes resulting from ZEN exposure (p < 0.01). Furthermore, the proteomic analysis demonstrated a notable upregulation of protein expression levels, specifically STAT2 (0.12 ± 0.0186), STAT6 (0.36 ± 0.0475) and ISG15 (0.43 ± 0.0226) in the rat colon (p < 0.05). Utilizing bioinformatics analysis, we combined ZEN exposure and IBD clinical sample databases to reveal that ZEN exposure may increase the risk of IBD through activation of the STAT-ISG15 pathway. This study identified novel targets for ZEN-induced intestinal toxicity, providing the basis for further study of ZEN exposure to IBD.

Lipids, lipid-lowering agents, and inflammatory bowel disease: a Mendelian randomization study.

To assess the causal role of lipid traits and lipid-lowering agents in inflammatory bowel disease (IBD). Univariable mendelian randomization (MR) and multivariable MR (MVMR) analyses were conducted to evaluate the causal association between low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and IBD. Drug-targeted MR analyzed the effects of lipid-lowering drugs on IBD, and network MR was used to analyze potential mediation effects. The levels of HDL-C had an inverse relationship with the risk of Crohn's disease (CD, OR: 0.85, 95% CI: 0.73-0.98, P = 0.024). In MVMR, the inverse relationships were found in all three outcomes. Drug-targeted MR analyses showed that with one-SD LDL-C decrease predicted by variants at or near proprotein convertase subtilisin/kexin type 9 (PCSK9), the OR values of people diagnosed with IBD, ulcerative colitis (UC) and CD were 1.75 (95%CI: 1.13-2.69, P = 0.011), 2.1 (95%CI: 1.28-3.42, P = 0.003) and 2.24 (95%CI: 1.11-4.5, P = 0.024), respectively. With one-SD LDL-C decrease predicted by variants at or near cholesteryl ester transfer protein (CETP), the OR value of people diagnosed with CD was 0.12 (95%CI: 0.03-0.51, P = 0.004). Network-MR showed that HDL-C mediated the causal pathway from variants at or near CETP to CD. Our study suggested a causal association between HDL-C and IBD, UC and CD. Genetically proxied inhibition of PCSK9 increased the risk of IBD, UC and CD, while inhibition of CETP decreased the risk of CD. Further studies are needed to clarify the long-term effect of lipid-lowering drugs on the gastrointestinal disorders.

The causal effects of inflammatory bowel disease on primary biliary cholangitis: A bidirectional two-sample Mendelian randomization study.

Observational studies have indicated that the incidence of primary biliary cholangitis (PBC) is higher in inflammatory bowel disease (IBD) patients than that in healthy people. However, whether the correlation is causal remains unclear. The genetic associations with IBD were obtained from publicly available genome-wide association studies (GWAS) of European ancestry with 31 665 cases and 33 977 controls, consisting of 17 897 Crohn's disease (CD) and 13 768 ulcerative colitis (UC) cases. The genetic associations with PBC were obtained from a European GWAS with 2764 cases and 10 475 controls. A bidirectional two-sample Mendelian randomization (MR) design was implemented to determine the causal relationship between IBD and PBC. In the forward MR, the IBD was treated as the exposure while the PBC was the exposure in the reverse MR. The inverse-variance-weighted (IVW) method was utilized as the main statistic method, and a series of sensitivity analyses were performed to detect heterogeneity and horizontal pleiotropy. A total of 99 valid instrumental variables (IVs) were selected for IBD and the number of IVs for PBC was 18. The forward MR analysis indicated that genetically predicted IBD (UC and CD) was significantly associated with an increased risk of PBC (IVW OR = 1.343; 95% CI: 1.220-1.466). Similar casual associations were observed in UC (IVW OR = 1.244; 95% CI: 1.057-1.430) and CD (IVW OR = 1.269; 95% CI: 1.159-1.379). Such results were still consistent in multiple MR methods. The reverse MR analysis implicated that genetic susceptibility to PBC might not alter the risk of IBD (IVW OR = 1.070; 95% CI: 0.984-1.164). Our study found that genetically predicted IBD can increase the risk of PBC while not vice versa in the European population, which may enlighten the aetiology of PBC, together with the IBD patient management.

Association between α-defensin 5 and the expression and function of P-glycoprotein in differentiated intestinal Caco-2 cells.

α-Defensin 5 is known to be secreted by Paneth cells in the small intestine and plays an important role in eliminating pathogenic microorganisms. It has been reported that a decrease in α-defensin 5 level in the human small intestine is a risk of inflammatory bowel disease (IBD). Furthermore, P-glycoprotein (P-gp), a member of the ATP-binding cassette transporter superfamily, encoded by the ABCB1/MDR1 gene, plays an important role in the front line of host defense by protecting the gastrointestinal barrier from xenobiotic accumulation and may contribute to the development and persistence of IBD. Therefore, we examined the relationship between α-defensin 5 and the expression and function of P-gp using a human gastrointestinal model cell line (Caco-2). We found that MDR1 mRNA and P-gp protein level were increased in Caco-2 cells as well as α-defensin 5 secretion corresponded with the duration of cell culture. Exposure to α-defensin 5 peptide and recombinant tumor necrosis factor-α (TNF-α) significantly increased the expression and function P-gp. The mRNA levels of interleukin (IL)-8, IL-6, TNF-α, IL-1β, and IL-2 were also increased following exposure to TNF-α, similar to α-defensin 5 treatment. These results suggest that α-defensin 5 regulates P-gp expression and function by increasing TNF-α expression in Caco-2 cells.

The rs9402373 polymorphism of CTGF gene may not be related to inflammatory bowel disease susceptibility in Chinese population based on ARMS-PCR genotyping

BackgroundIt has been confirmed that the connective tissue growth factor (CTGF) gene rs9402373 polymorphism is associated with fibrotic and inflammatory diseases. However, studies on the relationship between polymorphisms in CTGF rs9402373 and inflammatory bowel disease (IBD) remain rare. Therefore, the aim of this study was to assess the association between the CTGF rs9402373 polymorphism and IBD susceptibility in a Chinese population. Materials and methodsTo establish an amplification refractory mutation system (ARMS) PCR technology for genotyping CTGF gene rs9402373 polymorphism, we designed two specific forward primers for the wild and mutant types by placing the allele-specific nucleotide at the penultimate position of the ‘3′ end of the primer. Then, 10 samples were randomly selected and rechecked by DNA sequencing to verify the accuracy of this method. We further used the established method to detect specimens collected from 191 patients with inflammatory bowel disease, including 120 Crohn's disease (CD) and 71 ulcerative colitis (UC), and 110 healthy Han Chinese individuals. ResultsWe successfully established the ARMS-PCR method for genotyping, and the results of 10 randomly selected samples were completely consistent with DNA sequencing. The rs9402373 G allele frequencies in UC and CD cases were 38.03% and 43.75%, respectively, and in controls, they were 41.82%. No significant difference was found in minor allele frequencies between the UC or CD and control groups (P = 0.473, P = 0.676). Genotype analysis demonstrated that there was no relationship between CTGF rs9402373 polymorphism and the risk of IBD regardless of the inheritance mode (P > 0.05). ConclusionsIn this preliminary study, we successfully developed a simple, efficient and cost-effective method for genotyping CTGF rs9402373 polymorphism. The polymorphism may not be related to IBD susceptibility in the Chinese Han population.