Risk Of IBD Research Articles

Antibacterial exposure increases risk of IBD

Antibacterial exposure increases risk of IBD

Oral Spore-Based Probiotic Supplementation Alters Post-Prandial Expression of mRNA Associated with Gastrointestinal Health.

Background/Objectives: Unregulated post-prandial dietary endotoxemia may accumulate over time and underlie the development of chronic disease (e.g., leaky gut, inflammatory bowel disease, etc.), for which oral probiotic supplementation may be a prophylactic. The purpose of this study was to determine if 45 d of oral spore-based probiotic supplementation altered gastrointestinal-associated mRNA expression following a high-fat meal. Methods: A subset of apparently healthy individuals from a larger study who had dietary endotoxemia at baseline completed 45 d of supplementation with either a placebo (rice flour; n = 10) or spore-based probiotic (Megasporebiotic™; Novonesis, Kongens Lyngby, Denmark; Bacillus indicus (HU36™), Bacillus subtilis (HU58™), Bacillus coagulans (SC208™), and Bacillus licheniformis (SL-307), and Bacillus clausii (SC109™); n = 10). Venous blood was collected in Paxgene RNA tubes prior to (PRE), 3 h, and 5 h after consumption of a high-fat meal (85% of the daily fat RDA and 65% of the daily calorie needs). Total RNA was analyzed for 579 mRNAs of interest (Nanostring nCounter Sprint; Seattle, WA, USA). After normalization to housekeeping controls and calculation of differential expression relative to PRE and controlled for FDR, 15 mRNAs were determined to be significantly changed at either 3 h and/or 5 h post-prandial in the probiotic group but not in the placebo group. Results: Significant mRNA expressions were associated with gastrointestinal tract barrier function (four mRNAs: BATF3, CCR6, CXCR6, and PDCD2), gastrointestinal immunity (four mRNAs: CLEC5A, IL7, CARD9, and FCER1G), or future IBD risk (seven mRNAs: PD-L1, CSF1R, FAS, BID, FADD, GATA3, and KIR3DL). Conclusions: Collectively, the present findings may support the notion that post-prandial immune response to eating is enhanced following 45 d of probiotic supplementation.

The role of antibiotic exposure as risk factor for IBD epidemic: an updated meta-analysis.

The rising prevalence of IBD globally has raised concerns about antibiotic exposure. This study's meta-analysis examines antibiotic exposure, frequency, year before diagnosis, regional differences, and IBD incidence. The literature review used PubMed, Web of Science, Elsevier, ScienceDirect, and Cochrane CENTRAL databases up to June 2024 to explore the link between antibiotic exposure and IBD risk. Stratified analysis was conducted by years of antibiotic exposure before IBD diagnosis, frequency, and region. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were combined using a random effects model. Eighteen case-control studies and five cohort studies were included (n=99, 104 IBD patients and n=2 273 336 controls). The findings indicate that antibiotic exposure significantly has a positive association with the risk of developing IBD (OR, 1.66; 95% CI, 1.28-2.16). Antibiotic exposure of ≥3years (OR, 1.49; 95% CI, 1.12-1.98), 2years (OR, 1.46; 95% CI, 1.37-1.55), and ≤1year (OR, 1.55; 95% CI, 1.17-2.04) prior to the diagnosis of IBD is associated with a higher risk of developing IBD. Cumulative exposure of ≥3 dispensations (OR, 2.02; 95% CI, 1.49-2.74) and two dispensations (OR, 1.36; 95% CI, 1.03-1.78) also had a positive association with IBD risk, while one dispensation did not (OR, 0.96; 95% CI, 0.72-1.26). No significant association was found in developing countries (OR, 1.92; 95% CI, 0.71-5.19), but developed countries showed a significant positive association with the risk (OR, 1.58; 95% CI, 1.27-1.96). The meta-analysis suggests that antibiotic use has a positive association with the risk of IBD, and limiting unnecessary antibiotic use may be one way to reduce the risk of developing IBD.

Impact of prenatal and postnatal maternal IBD status on offspring’s risk of IBD: a population-based cohort study

ObjectiveIn utero exposure to maternal inflammation may impact immune system development and subsequent risk of disease. We investigated whether a maternal diagnosis of IBD before childbirth is linked to a...

Inflammatory bowel disease associated with primary sclerosing cholangitis is associated with an altered gut microbiome and bile acid profile.

Primary sclerosing cholangitis associated with inflammatory bowel disease (IBD-PSC) carries significant morbidity compared to IBD without PSC. Alterations in microbial composition and bile acid (BA) profiles have been shown to modulate chronic inflammation in IBD, but data in IBD-PSC is scarce. We aimed to assess the differences in gut microbiome composition as well as in the BA profile and BA-related microbial functions between IBD-PSC and IBD-only. 54 IBD-PSC and 62 IBD-only subjects were enrolled from 2012 to 2021. Baseline samples were collected for fecal DNA shotgun metagenomic sequencing, fecal and serum BA quantitation using mass spectrometry and fecal calprotectin. Liver fibrosis measured by transient elastography (TE) was assessed in the IBD-PSC group. Data was analyzed using general linear regression models and Spearman rank correlation tests. Patients with IBD-PSC had reduced microbial gene richness (p=0.004) and significant compositional shifts (PERMANOVA: R2=0.01, p=0.03) compared to IBD-only. IBD-PSC was associated with altered microbial composition and function, including decreased abundance of Blautia obeum, increased abundance of Veillonella atypica, Veillonella dispar and Clostridium scindens (q<0.05 for all), and increased abundance of microbial genes involved in secondary BA metabolism. Decreased serum sulfated and increased serum conjugated secondary BA were associated with IBD-PSC and increased liver fibrosis. We identified differences in microbial species, functional capacity and serum BA profiles in IBD-PSC compared with IBD-only. Our findings provide insight into the pathophysiology of IBD associated with PSC and suggest possible targets for modulating the risk and course of IBD in subjects with PSC.

Farming Activities and Risk of Inflammatory Bowel Disease: A French Nationwide Population-based Cohort Study.

Epidemiological data regarding inflammatory bowel disease [IBD] are lacking, in particular for occupationally exposed populations. We investigated whether, among the entire French farm manager [FM] workforce, certain agricultural activities are more strongly associated with IBD than others. Nationwide, population-based, insurance claims and electronic health records from all FMs who worked at least once over the period 2002-2016 were used [n = 1 088 561, 69% males]. The outcome measure was the association between 26 farming activities and the risk of IBD, Crohn's disease [CD], and ulcerative colitis [UC], measured as hazard ratios [HRs], after adjusting for age, sex, pre-existing medical comorbidities, and farm location. The time to first chronic disease declaration was used as the underlying time scale. A model was generated for every activity and disease, using a reference group comprising all FMs who abstained from the specified activity from 2002 to 2016. There were 1752 IBD cases, with 704 CD [40.2%] and 1048 UC [59.8%] cases, respectively. Elevated HRs were observed for fruit arboriculture [HR from 1.17 to 1.52] and dairy farming [HR from 1.22 to 1.46] for all IBD, in crop farming for CD only (HR = 1.26, 95% confidence interval [CI]: 1.06-1.49), and in shellfish farming [HR from 2.12 to 2.51] for both CD and IBD. Further research regarding specific farming activities and exposures likely to modify the microbiota [eg, pesticides, pathogens] is required to identify potential occupational risk factors [agricultural exposome] for IBD. Exposure to Mycobacterium avium subspecies paratuberculosis, Cryptosporidium, environmental toxins, micro/nanoplastics, and pesticides represents promising research avenues.

Association between inflammatory bowel disease and cancer risk: evidence triangulation from genetic correlation, Mendelian randomization, and colocalization analyses across East Asian and European populations

BackgroundInflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), has been associated with several cancer risks in observational studies, but the observed associations have been inconsistent and may face the bias of confounding and reverse causality. The potential causal relationships between IBD and the risk of cancers remain largely unclear.MethodsWe performed genome-wide linkage disequilibrium score regression (LDSC), standard two-sample Mendelian randomization (MR), and colocalization analyses using summary genome-wide association study (GWAS) data across East Asian and European populations to evaluate the causal relationships between IBD and cancers. Sensitivity analyses for the MR approach were additionally performed to explore the stability of the results.ResultsThere were no significant genetic correlations between IBD, CD, or UC and cancers (all P values > 0.05) in East Asian or European populations. According to the main MR analysis, no significant causal relationship was observed between IBD and cancers in the East Asian population. There were significant associations between CD and ovarian cancer (odds ratio [OR] = 0.898, 95% CI = 0.844–0.955) and between UC and nonmelanoma skin cancer (OR = 1.002, 95% CI = 1.000–1.004, P = 0.019) in the European population. The multivariable MR analysis did not find any of the above significant associations. There was no shared causal variant to prove the associations of IBD, CD, or UC with cancers in East Asian or European populations using colocalization analysis.ConclusionsWe did not provide robust genetic evidence of causal associations between IBD and cancer risk. Exposure to IBD might not independently contribute to the risk of cancers, and the increased risk of cancers observed in observational studies might be attributed to factors accompanying the diagnosis of IBD.

The effect of air pollution on the risk of inflammatory bowel disease, colorectal cancer and appendicitis

Introduction and objective&#x0D; Intense industrial development is contributing to increased emissions of air pollutants. Numerous studies indicate a link between air pollution and a higher risk of pulmonary and cardiovascular diseases. Our goal is to analyze available scientific studies to demonstrate the relationship between air pollution and the risk of developing and complicating inflammatory bowel disease, colorectal cancer and appendicitis.&#x0D; Brief description of the state of knowledge&#x0D; Air pollution is a global health challenge. Particles such as PM, nitrogen oxides, sulfur oxides or ozone have a significant impact on health. Studies suggest a link between pollution and intestinal diseases (IBD, CRC, appendicitis). Air pollutants can affect the gut by causing inflammation, oxidative stress and disruption of the gut microbiota. Exposure to PM2.5 can increase the risk of IBD, CRC, and PM10 can increase the risk of UC. There is a correlation between pollution and the rate of hospitalization for IBD. In addition, exposure to PM2.5 increases the risk of colorectal cancer mortality. Short-term exposure to air pollution is associated with more hospitalizations for appendicitis.&#x0D; Summary&#x0D; Air pollution is a real health risk. Reducing air pollution could potentially reduce the risk of developing these intestinal diseases and their complications. Despite the potential links, further research is required to better understand the mechanisms of action of pollutants on intestinal health. Urgent and coordinated global and local action is needed to reduce air pollution emissions and protect the health of the public.

Tobacco Smoke Exposure in Early Childhood and Later Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

To examine the association between early-life smoking exposure and later risk of inflammatory bowel disease [IBD]. We followed 115663 participants from the Norwegian Mother, Father and Child [MoBa] and All Babies in Southeast Sweden [ABIS] cohorts from birth [1997-2009] through 2021. IBD was identified through national patient registers. Validated questionnaire data defined maternal smoking during pregnancy, maternal environmental tobacco smoke [ETS] exposure during pregnancy, and child ETS exposure by ages 12 and 36 months. Cox regression was used to estimate adjusted hazard ratios [aHRs] for sex, maternal age, education level, parental IBD, and origin. Cohort-specific estimates were pooled using a random-effects model. During 1 987 430 person-years of follow-up, 444 participants developed IBD [ABIS, 112; MoBa, 332]. Any vs no maternal smoking during pregnancy yielded a pooled aHR of 1.30 [95% CI = 0.97-1.74] for offspring IBD. Higher level of maternal smoking during pregnancy (compared with no smoking, average ≥6 cigarettes/day: pooled aHR = 1.60 [95% CI = 1.08-2.38]) was associated with offspring IBD, whereas a lower smoking level was not (average 1-5 cigarettes/day: pooled aHR = 1.09 [95% CI = 0.73-1.64]). Child ETS exposure in the first year of life was associated with later IBD (any vs no ETS, pooled aHR = 1.32 [95% CI = 1.03-1.69]). Estimates observed for child ETS exposure by 36 months were similar but not statistically significant. In this prospective Scandinavian cohort study, children exposed to higher levels of maternal smoking during pregnancy or ETS during the first year of life were at increased risk of later IBD.

P1191 Genetic determinants for smoking behaviour improve our understanding of sporadic versus familial Inflammatory Bowel Disease

Abstract Background Inflammatory bowel disease (IBD) is influenced by genetic and environmental factors. The latter are often difficult to quantify and may vary over time, unlike genetics. Here, instead of looking at actual smoking behaviour, we explored the impact of genetic determinants of smoking behaviour on IBD risk in sporadic and familial IBD. Methods We calculated polygenic scores (PRS) for smoking initiation, smoking cessation, age of smoking initiation, and cigarettes per day in 2784 sporadic cases (1700 CD, 1084 UC), 682 non-IBD controls, and 60 multiplex IBD families with ≥3 affected first-degree relatives (FDR) (142 CD, 31 UC and 100 unaffected FDR). PRS were calculated for different p-value thresholds (5e-8, 1e-5, 0.01, 0.05, 0.1, 0.5 and 1), and based on effect estimates of Saunders et al (Nature 2022, table 1). Groups were compared using logistic regression. P&amp;lt;1.43e-3 was the significance threshold for Bonferroni correction. Results Sporadic IBD cases had a higher PRS for smoking initiation than controls (p=4.49e-3), which was driven by the CD cases (p=7.17e-4, fig 1A). CD cases also showed a trend for a higher PRS for cigarettes per day (p=0.026). In familial cases compared to unaffected FDR, we observed some differences in PRS for smoking, but none survived multiple testing (fig 1B). Comparing familial and sporadic cases, we found that the PRS for age at smoking initiation was higher in familial than in sporadic UC (p=9.09e-4, fig 1C). Familial CD showed a trend towards a lower PRS for age at smoking initiation (p=0.023) and smoking cessation (p=0.013) than sporadic CD. Familial CD cases are thus more at risk than sporadic CD cases as they genetically tend to start smoking younger, while the opposite is seen for UC. Also, unaffected FDR of UC families showed a lower PRS for age at smoking initiation (p=5.47e-5, fig 1D) than controls, giving them additional protection. The PRS for smoking cessation (p=3.88e-5) and cigarettes per day (p=4.47e-3) was greater in unaffected FDR of mixed families than in controls, while familial mixed cases had a lower cigarettes per day PRS than sporadic cases (p=1.59e-4). Conclusion We found that genetic determinants of smoking behaviour are associated with disease risk in familial and sporadic IBD. While CD risk overall is associated with a greater genetic propensity for smoking initiation, the higher risk in families is linked to genetic age at start of smoking. Meanwhile, unaffected FDR of these families are protected through a higher genetic propensity to stop smoking in mixed families, or to start smoking sooner in UC families, compared to population controls. This study improves our understanding of familial vs sporadic IBD, and could help stratify individuals at risk of IBD.

Early-life diet and risk of inflammatory bowel disease: a pooled study in two Scandinavian birth cohorts

ObjectiveWe assessed whether early-life diet quality and food intake frequencies were associated with subsequent IBD.DesignProspectively recorded 1-year and 3-year questionnaires in children from the All Babies in Southeast Sweden and...

Exploring inflammatory bowel disease therapy targets through druggability genes: a Mendelian randomization study.

Inflammatory bowel disease is an incurable group of recurrent inflammatory diseases of the intestine. Mendelian randomization has been utilized in the development of drugs for disease treatment, including the therapeutic targets for IBD that are identified through drug-targeted MR. Two-sample MR was employed to explore the cause-and-effect relationship between multiple genes and IBD and its subtypes ulcerative colitis and Crohn's disease, and replication MR was utilized to validate this causality. Summary data-based Mendelian randomization analysis was performed to enhance the robustness of the outcomes, while Bayesian co-localization provided strong evidential support. Finally, the value of potential therapeutic target applications was determined by using the estimation of druggability. With our investigation, we identified target genes associated with the risk of IBD and its subtypes UC and CD. These include the genes GPBAR1, IL1RL1, PRKCB, and PNMT, which are associated with IBD risk, IL1RL1, with a protective effect against CD risk, and GPX1, GPBAR1, and PNMT, which are involved in UC risk. In a word, this study identified several potential therapeutic targets associated with the risk of IBD and its subtypes, offering new insights into the development of therapeutic agents for IBD.

Colonization of larval zebrafish (Danio rerio) with adherent-invasive Escherichia coli prevents recovery of the intestinal mucosa from drug-induced enterocolitis.

Although inflammatory bowel diseases are on the rise, what factors influence IBD risk and severity, and the underlying mechanisms remain to be fully understood. Although host genetics, microbiome, and environmental factors have all been shown to correlate with the development of IBD, cause and effect are difficult to disentangle in this context. For example, AIEC is a known pathobiont found in IBD patients, but it remains unclear if gut inflammation during IBD facilitates colonization with AIEC, or if AIEC colonization makes the host more susceptible to pro-inflammatory stimuli. It is critical to understand the mechanisms that contribute to AIEC infections in a susceptible host in order to develop successful therapeutics. Here, we show that the larval zebrafish model recapitulates key features of AIEC infections in other animal models and can be utilized to address these gaps in knowledge.

Frailty and pre-frailty with long-term risk of elderly-onset inflammatory bowel disease: A large-scale prospective cohort study

PurposeTo investigate the prospective association of frailty status with the long-term risk of elderly-onset IBD in a large prospective cohort. MethodsParticipants free of IBD and cancer at enrollment from the UK Biobank cohort were included. Baseline pre-frail and frail status was measured by Fried phenotype including weight loss, exhaustion, low grip strength, low physical activity and slow walking pace, defined as meeting one or two criteria and meeting three or more criteria. Primary outcome was elderly-onset IBD, including elderly-onset ulcerative colitis (UC) and Crohn’s disease (CD). Multivariable Cox regression was conducted to examine the related associations. ResultsOverall, 417,253 participants (aged 56.18 ± 8.09 years) were included. Of whom, 19,243 (4.6 %) and 188,219 (45.1 %) were considered frail and pre-frail, respectively. During a median of 12.4 years follow-up, 1503 elderly-onset IBD cases (1001 UC, 413 CD, and 89 IBD-Unclassified) were identified. Compared with non-frail, individuals with frail (HR=1.40, 95 %CI: 1.13–1.73) and pre-frail (HR=1.15, 1.03–1.28) showed significantly higher risk of elderly-onset IBD after multivariable adjustment (Ptrend<0.001). The positive association was more evident regarding risk of elderly-onset CD (HR=2.16, 1.49–3.13 for frail; HR=1.49,1.20–1.85 for pre-frail; Ptrend<0.001). Sensitivity analyses and subgroup analyses according to age, gender and body mass index (BMI) demonstrated similar results. ConclusionsFrailty and pre-frailty are associated with increased risk of elderly-onset IBD, particularly elderly-onset CD.

S1053 Childhood Obesity Increases Risk of Adult-Onset IBD, but Adult-Onset Obesity May Lead to Worse Disease Outcomes

S1053 Childhood Obesity Increases Risk of Adult-Onset IBD, but Adult-Onset Obesity May Lead to Worse Disease Outcomes

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.

Genetically predicted levels of folate, vitamin B12, and risk of autoimmune diseases: A Mendelian randomization study.

Evidence from observational studies on the association of folate and vitamin B12 with autoimmune diseases are conflicting. We aimed to investigate the relationship of folate and vitamin B12 with autoimmune diseases using Mendelian randomization (MR). We selected single-nucleotide polymorphisms associated with folate and vitamin B12 at the genome-wide significance level. Summary-level data for four common autoimmune diseases (vitiligo, inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus) were obtained from large-scale genome-wide association studies, with a sample size of 44,266, 86,640, 58,284, and 23,210, respectively. MR analyses were conducted using the inverse variance weighted (IVW) approach, and sensitivity analyses were further performed to test the robustness. We found that a higher genetically determined serum folate level per one standard deviation (SD) was associated with a decreased risk of vitiligo by the IVW method [odds ratios (OR) = 0.47; 95% confidence interval (CI): 0.32-0.69; P = 1.33 × 10-4]. Sensitivity analyses using alternative methods showed similar associations, and no evidence of pleiotropy was detected by MR-Egger regression (P = 0.919). In addition, we observed that vitamin B12 per one SD was positively associated with IBD (IVW: OR = 1.14, 95% CI: 1.03-1.26, P = 0.010; maximum likelihood: OR = 1.14, 95% CI: 1.01-1.29, P = 0.035; MR-PRESSO: OR = 1.14, 95% CI:1.01-1.28, P =0.037), while the association was not significant after Bonferroni correction. The study provides convincing evidence for an inverse association between serum folate level and risk of vitiligo. Further studies are warranted to elucidate the possible association between vitamin B12 and risk of IBD.

A87 PERSPECTIVES ON DIET MODIFICATION TO MANAGE THEIR SYMPTOMS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE. A SCOPING REVIEW

Abstract Background The link between diet, disease activity and symptoms in IBD patients have recently gained attention and recommendations on dietary interventions to manage symptoms are common. Most studies have explored the correlation between dietary patterns and increased risk of IBD or symptom severity. However, there is limited understanding and no relevant systematic review of IBD patients’ perspectives and barriers to adopt the prescribed diets. We thus conducted a scoping review for this topic. Purpose Aim: We performed a scoping review of current evidence to investigate the extent of evidence on IBD adult patients’ perspectives on dietary modification to manage their symptoms and gaps for future research to explore patients' experiences. Method We followed the JBI (Joanna Briggs Institute) method for scoping reviews. A systematic search of Ovid Medline, Embase and Cochrane Library was conducted in April 2022 to retrieve published English language qualitative, quantitative and mixed methods studies that report IBD patients’ perspectives, behaviours, beliefs related to diet modification and barriers to diet adoption for managing their symptoms or disease activity. We manually reviewed reference lists of reviews on this topic. Since this is a scoping review, no statistical comparison is needed. Result(s) Out of 2822 papers screened, 42 studies met the inclusion criteria. Various methods were used in included studies with heterogenous outcomes reported. Of the 42 studies, 19 reported IBD patients' beliefs and behaviors related to diet as a primary outcome. Most patients reported changing their diet after being diagnosed with IBD, and food avoidance and restrictive diet were commonly reported to prevent relapse. Some studies reported that many patients reduced their opportunities for social life, such as eating out, practicing outdoor sports, having dinner with family in the same household and meeting friends. The dietary modification was more significant among individuals with active than inactive disease. Most studies showed that patients believe food can play a role in causing or preventing relapse, but beliefs are varied regarding the role of diet as initiating factor for IBD. Some patients believe dietary modification could be more important than medication to manage their disease symptoms. Few studies focused on patients' barriers when changing their diet, but financial barriers and limited nutritional guidance were commonly reported acknowledging searching for dietary advice on the internet. Conclusion(s) Food avoidance and social restriction for relapse prevention are standard practices by most IBD patients. The belief that nutrition is key in managing IBD is prevalent. This scoping review highlights the need to identify patients' barriers to accessing professional dietary guidance and nutritional interventions and provides direction for clinical studies and systematic reviews of focused research questions. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

P906 Prevalence and CARD9 IBD risk variant rs4077515 in a Chilean IBD Cohort

Abstract Background Genome-wide association studies (GWAS) have identified hundreds of polymorphisms associated with an increased risk of developing IBD. Among risk genes identified by GWAS, CARD9, a gene encoding an adapter molecule involved in the innate immune response to fungi and bacteria, has been related to IBD risk. CARD9 alleles in IBD patients may have either a protective function or a high genetic risk factor such as rs4077515. Interestingly, the CARD9S12N (rs4077515) variant has a higher frequency in the Latin South American population than the Caucasian population. The relevance of rs4077515 in the risk of IBD in the Latino population is unknown. Aims (1) To estimate allele and genotype frequencies for rs4077515 in IBD patients and Chilean controls and compare with Ensembl genome database (public data available). (2) To compare the allele and genotype distributions in IBD patients and controls, including association tests and estimation of ORs according to additive, dominant and recessive penetrance models. Methods 260 IBD patients were genotyped using the TaqMan SNP genotyping technology based on qPCR. Aggregated genotype information for 3147 population-based Chilean controls was retrieved from a published study on gallstones in Chileans (Lorenzo et al., Hepatology 2021). We calculated the allele and genotype frequencies for rs4077515 and then compared these frequencies with controls. A Chi-square test of association was used under the null hypothesis of no association between genotypes and disease. Univariate and multiple logistic regression were performed (additive, dominant, and recessive penetrance models). Results Table 1 compares rs4077515 allele and genotype frequencies in Chileans and other populations (Ensembl data set). Table 2. exhibits the estimated odds ratio for IBD, CD, and UC in Chilean population. Table 3. reveals the association results for rs4077151 models in the Chilean population. Conclusion In this study, the A risk allele for rs4077515 is significantly more frequent in the Chilean population than reported in other populations such as European, but similar to Amerindian. In this Chilean cohort, the variant rs4077515 is not associated with higher IBD risk. However, this could be an effect of sample size, or patients carrying rs4077515 requires an additional factor to IBD development.

P881 Is occupation a risk factor for developing Inflammatory Bowel Disease? A case-control study

Abstract Background The role of occupation is well established for different diseases. Nevertheless, there is a lack of information on the role of occupation on the onset of inflammatory bowel diseases. Many occupations entail the exposure of different toxic substances that may reach the bowel through different biological pathways (bloodstream or digestive tract) and act as possible triggers of such diseases, mainly Crohn′s disease and ulcerative colitis. The aim of this study is to identify if there is a role of occupation on the onset of IBD using a case-control study. Methods A prospective case-control, single-center study was designed. All Incident cases with any of the main IBD diseases (ulcerative colitis, Crohn’s disease and unclassified colitis) were consecutively included. Controls were patients selected from the consults and endoscopic room of the Digestive Unit of Clinical Hospital of Santiago de Compostela without any autoimmune chronic disease. Cases are patients with IBD disease diagnosed 3 or less months prior to the inclusion and over 18 years old. Cases and controls were recruited simultaneously and controls followed a sex and age frequency matching with cases. All participants were recruited from June 2020 to September 2022. A detailed questionnaire describing the occupations held and time of them was used. Blue-collar jobs have been defined as those entailing the highest risk occupational exposures and are also mentioned as manual workers. White-collar jobs are usually those with more office-related work, but also with teaching or health sector. To analyze the results, we used a logistic regression. A subgroup analysis was performed by each of the three diseases considered. Results 129 patients with incident IBD (73 with ulcerative colitis, 51 with Crohn’s disease and 5 with indeterminate colitis) and 114 controls were included. Comparing patients with IBD with controls, there were no statistically significant differences between type of work, working hours, contact with animals or physical activity at work. Among the patients with IBD, there were no differences in the number of flares between groups (blue collar workers vs. white collar (p&amp;gt;0.05), outside workers vs. indoor ones (p&amp;gt;0.05), sedentariness vs. moderate activity or high activity (p&amp;gt;0.05) or animal contact vs. no contact (p&amp;gt;0.05)). Taking into account only patients with current work activity, the results did not change. After stratifying results according to type of IBD, there were no statistically significant differences either (table 1). Conclusion In this study, differences between type of work, working hours, contact with animals or sedentariness were not associated with the risk of IBD nor with the activity of this disease.