Incidence Of IBD Research Articles

P892 Characteristics and trend of Inflammatory Bowel Disease epidemiology for 30 years from 1991 to 2020: A single-center experience analysis in Incheon, Korea

Abstract Background Inflammatory bowel disease (IBD) in Asia is different from that of the West in incidence, prevalence, clinical features, and genetic mutations. The purpose of this study was to investigate changes in the characteristics and trends in patients with IBD over 30 years in a single center in Incheon, Korea. Methods Among 1,070 IBD patients (Crohn’s disease [CD] 286; ulcerative colitis [UC] 784) who visited from Jan 1991 to Dec 2020, 773 patients (CD 204; UC 569) who were first diagnosed and followed for more than 1 year were enrolled. The demographic characteristics and trends of IBD patients for 30 years of IBD were analyzed retrospectively by dividing them into three periods. Results In CD, the age at diagnosis gradually decreased from 24.7±5.1 years in 1990-2000 to 21.9±9.5 years in 2011-2020 (p-trend=0.025), but there was no significant change in UC (p-trend=0.177). The male-to-female ratio showed a tendency to increase from 0.7 to 1.5 in UC (p-trend=0.002) over 30 years. The UC/CD ratio gradually decreased from 6.4 in 1991-2000, 2.6 in 2001-2010, and 2.5 in 2011-2020. In CD, the colonic phenotype gradually decreased with the recent period (35.7%, 26.2%, and 15.2%, respectively; p<0.01), but there was no difference in disease behavior (p=0.482). At the time of diagnosis, 35.8% of CD patients had a history of perianal abscess/fistula. In UC, there was no change in disease extent according to the periods, and the overall proctitis, left-sided, and pancolitis were 46.2%, 30.2%, and 23.6%, respectively. For the severity of UC, mild disease gradually increased; by 34.4% in 1991-2000, 47.0% in 2001-2010, and 60.1% in 2011-2020, respectively (p<0.001). Conclusion The incidence and prevalence of IBD in Korea have continued to increase over the past three decades. Age, male-to-female ratio, phenotype, and severity at the time of diagnosis of IBD in Korea are constantly changing.

DOP60 Environmental risk factors for Inflammatory bowel disease: A large prospective case-control study in India

Abstract Background Increasing urbanization and westernization of lifestyles have been implicated for the rising incidence of IBD in the developing world. However real world data is very limited. We planned a comprehensive assessment of environmental exposures in a large cohort of patients with and without IBD in India to identify key risk factors. Methods This study is a part of a wider epidemiologic colonoscopic screening program for detection of IBD on all symptomatic patients attending the hospital and specially conducted rural health camps. A detailed questionnaire based survey of environmental risk factors including diet, smoking, antibiotic use, hygiene status, microbial exposures, vaccination, water supply, rural/urban residence was conducted prior to colonoscopy. The risk factors were compared among the IBD and non IBD patients with normal colonoscopy. Univariate logistic regression was done initially adjusting for age and sex followed by multivariate analysis to estimate adjusted ORs (aOR) and 95% CIs. Results 13421 completed environmental risk questionnaire.1306 IBD(576 CD;730 UC) cases diagnosed.12115 with normal colonoscopy served as the controls. In multivariate model, current smoking(aOR 5.66; 95% CI 4.41-7.26),ex-smoking (aOR 1.79;1.24-2.58), regular alcohol intake (aOR 1.82, 1.14-2.9), non-vegetarian diet(aOR 1.8; 1.48-2.23),daily bakery/fast food consumption(aOR 1.57; 1.31-1.88),soft drink consumption(> 2/week)(aOR 1.37,1.14-1.66), delivery by cesarean section (aOR 1.49, 95% CI 1.28-1.76), antibiotic use(<1 yr age) (aOR1.33;1.1-1.58), exposure to pets(aOR 1.68;1.39-2.03), Western toilets (aOR3.52, 2.56-3.58)and childhood infections (aOR 1.74; 1.45-2.028) increased risk of UC (Fig 1, 2). Increased risk of CD was seen with current smoking(aOR 6.16; 95% CI 4.68-8.11), ex-smoking(aOR2.15; 1.43-3.22),non-vegetarian diet (aOR 1.69;1.34-2.13), soft drink consumption(> 2/week)(aOR 1.84,1.51-2.24),daily bakery/fast food consumption(aOR 2.24;1.85-2.71), oral contraceptive pill use (aOR 3.79, 1.29-12.17) antibiotic use (<1 year age)(aOR 1.27; 1.04-1.54),exposure to pets(aOR 1.79; 1.45-2.2), caesarean section(aOR 1.48;1.23-1.77), Western toilets (aOR 2.98, 2.47-3.59), non-human milk exposure (<6 months age) (aOR 1.28, 1.03-1.6) and childhood infections(aOR 2.51; 2.1-3.04)(Fig 3, 4). Breastfeeding >6 months, daily fruit consumption and daily exercise were protective for both UC and CD (Fig1-4).Rural habitat was not protective for development of IBD both UC and CD. Conclusion This large prospective case control study of IBD risk factors in India identifies environmental triggers including childhood immunological, hygiene and dietary factors which modulate risk of IBD later in life.

P896 Inflammatory Bowel Disease in the elderly, a survey of elderly patient demographics, disease-related complications and compliance with vaccination and screening services

Abstract Background Inflammatory Bowel Disease (IBD) in the elderly (>60yrs) is becoming more prevalent in concordance with the ageing population and the rising incidence of IBD. An increasing number of patients are receiving a diagnosis of IBD in later years in addition to those with known IBD transitioning to elderly. The presentation, disease course, risk of complications and choice of medical therapies differ in this group from younger cohorts. We aimed to examine patient demographics and the incidence of adverse effects/complications amongst elderly IBD patients. We also sought to identify appropriate vaccination rates and uptake with screening services. Methods In a single tertiary centre, IBD patients aged >60 attending the outpatient clinic or admitted acutely were invited to complete an anonymous written survey. Results 28 patients surveyed to date. 61% (n=17) had a diagnosis of UC. 54% were female (n=15). Mean age was 67.5, while mean age at diagnosis was 50 (range 19-65). 25% (n=7) received a diagnosis of IBD after 60 years, of which 57% were female. Mean BMI was 25.9. 25% (n=7) reported an infection in the last 6 months, all of whom required treatment with antibiotics. There was only one case of infection requiring hospitilisation, a patient on biologic therapy who developed a clostridium difficile infection. COVID-19 affected 39% (n=11), none required hospitilisation. 21% (n=6) report 2 or more comorbidities, of which 50% report a recent infection requiring treatment. All patients who required IBD surgery (n=5) had a high BMI. 57% (n=16) had a smoking history, with 14% (n=4) being active smokers. Infliximab and salofalk granules were the most prescribed IBD treatments. 46% were on biologics (n=13), with anti-TNF being the most common (29%). 25% (n=7) reported steroid use in the last year while 14% were not currently on IBD treatment. 21.4% (n=6) reported prior malignancy, skin cancer being most common. 50% of cancer sufferers were smokers. 100% have had a minimal of two COVID-19 vaccines. 64% (n=18) have had a flu-vaccine in the last 12 months with 75% (n=21) report annual flu-vaccine uptake. 61% (n=17) had the pneumococcal vaccine. Bowel screening participation was 46.5% (n=13). Conclusion Smoking, high BMI and multiple comorbidities were common in elderly IBD patients. Infections were common in this cohort and typically required treatment with antibiotics, however, were rarely severe or required hospitalisation. Severe infections were seen in those on biologic therapy. Biologics were commonly prescribed to elderly IBD patients. Skin cancer was the most common malignancy. There was suboptimal uptake with vaccinations and bowel screening.

SURGICAL INTERVENTION IN PATIENTS WITH IDIOPATHIC INFLAMMATORY BOWEL DISEASE AND PERIANAL DISEASE

Aim: The aim of the study was to investigate the incidence of IBD in gastrointestinal surgery patients and record the disease’s characteristics and treatment. Materials and Methods: A search was carried out in the archives of the gastroenterology clinics of the University General Hospital of Ioannina and the General Hospital of Ioannina “G. Hatzikosta” in Greece. All cases of operated patients from 1980 to 2018 were examined. The duration of the study was 4 months. Data were analyzed with the SPSS program, v.28. Results: The total sample consisted of 1464 patients (n=1464). Most of them (915-62.5%) came from the University General Hospital of Ioannina, while the rest (549-37.5%) came from the GHI hospital “G. Hatzikosta”. The mean age of the patients was 47 years (M=47.26, SD=17.34, Min=<1 month, Max=95 years). From the total sample, 58 patients (4%) suffered from IBD; most were men (42-72.41%). Their mean age was approximately 50 years (M=49.63, SD=16.48, Min=25 years, Max=77 years, range=52 years) and most belonged to the age groups of 31-40 years (11 patients- 19.6%) and 21-30 years and 61-70 years (10 patients-17.9%). The perianal disease was present in 43.1% (25 patients). The most frequent type of operation was fistula resection, ligation, curettage-biopsy (24.1%) and opening-drainage (22.4%-13 patients) and the most frequent type of anesthesia was general anesthesia (93.1%-54 patients). Conclusions: This long-term study of the patients’ data followed up over time showed that the possibility of surgery in patients with IBD is mitigated through systematic monitoring and multifaceted therapeutic treatment.The perianal disease which appeared more often in men shows that it can be diagnosed early and at an early stage and with the new minimally invasive techniques the patient with IBD can be treated with a better quality of life.

Correlation incidence between infectious bursal disease and aflatoxicosis in broilers chicken farms in Nineveh province, Iraq

This study aimed to investigate the incidence of infectious bursal disease IBD and aflatoxicosis with the correlation between them in broilers of six different areas in Nineveh Province, Iraq, which include: Mosul, Talafer, Hamdanya, Bartella, Baaj, and Gayara for six months (October 2021-March 2022). The necropsy of the suspected infected birds and blood sampling were conducted on 25 birds for each area to diagnose IBD. Samples of broiler feed were collected from the same farms to diagnose aflatoxin B1. The detection of both IBD and aflatoxicosis occurred by the ELISA technique. The necropsy results showed hydropericardium, paleness or congestion, friable and swelling of the liver, kidneys, and bursa of Fabricius, with more severe lesions in a few sporadic cases as gelatinous fluid surrounding the heart, intense paleness of the liver, kidney, and enlarged bursa of Fabricius. The detection of IBD revealed that the positive results were 142, and the negative results are 8 birds out of a total of 150 suspected broiler attributed to the subclinical infection according to the vaccine index equation. Also, positive aflatoxin B1 concentrations were recorded in all broiler feed in the 6 areas as the highest concentration mean was 0.23 ppb and the lowest concentration mean was 0.186 ppb in Mosul and Baaj, respectively. This study indicated a positive correlation between IBD and aflatoxin B1 but was not statistically significant.

S124 Antibiotic Exposure Before 2 Years of Age is Associated With Increased Risk of Pediatric IBD in a Norwegian Nation-Wide Study

Background: The incidence of pediatric IBD (PIBD) rises. This development is likely related to environmental factors that cause disturbances in the gut microbiota. The infant’s microbiome is shaped among other factors by exposure to the maternal microbiome and reaches adult diversity around 3 years age. Antibiotics impact the developing microbiome. Earlier studies have shown an association between PIBD and postnatal antibiotic exposure but lack information on prenatal antibiotic exposure and potential confounders. Thus, the primary aim of this study was to determine whether prenatal antibiotic exposure and antibiotics the first 2 years of life are independently associated with subsequent PIBD, before a mature and stabilized gut microbiome is established. Methods: We conducted a nationwide register-based cohort study using data from the Norwegian Patient Registry to identify children with pediatric IBD <18 years born from 2004 to 2012. Dispensed antibiotics were retrieved from the Norwegian Prescription Database, and the Medical Birth Registry of Norway and Statistics Norway contributed with potential confounding factors. The unique personal ID number given to all new-born in Norway was used to connect the registers. All children were followed until December 31, 2020. We analyzed whether use of pre- and postnatal antibiotics until 2 years of age were associated with subsequent IBD by logistic regression adjusted for potential confounders. Results: The study-population included 536,821 children; 758 were classified as PIBD cases distributed as: 403 (53%) Crohn`s Disease, 243 (32%) Ulcerative Colitis and 112 (15%). IBD Unclassified. The IBD cases included 423 boys and 335 girls with a male predominance among the CD cases (2.2: 1). In the main analysis, sex-adjusted odds ratio (aOR) for developing IBD when exposed to antibiotics before 2 years of age compared to no exposure was 1.40 (95% CI: 1.21-1.61). After adjustment for prenatal antibiotic exposure the aOR was 1.39 (95% 1.20-1.59). Further adjustments for potential confounders as mode of delivery, preeclampsia, birthweight and gestational age, season of birth and maternal age, education, smoking, and parity did not change the OR estimates more than +/- 0.01. We found the strongest association for ≥2 courses of antibiotic exposures (aOR 2.14 (95% 1.34-3.43) and for broad-spectrum AB (aOR 2.36 95%CI: 1.45-3.83) compared to no exposure. This association was driven by the CD cases (aOR 1.59 with 95%CI: 1.31-1.94 P<0.01) while no significant association to antibiotic exposure was observed for the UC cases (aOR 1.12 95%CI: 0.87-1.44 P=0.89). Antibiotic exposure during the last trimester was associated with offspring PIBD (aOR 1.23 95%CI: 1.01-1.51), but this association was borderline significant after adjustment for postnatal antibiotic exposure (P = 0.07). Conclusion(s): In a nation-wide, register-based study from Norway, children exposed to antibiotics before 2 years of age were 1.4 -fold more likely to develop IBD before the age 18 years than controls. This association was found for CD only and was robust to adjustments for prenatal antibiotic exposures and other potential confounders.

Increasing Incidence of Inflammatory Bowel Disease, with Greatest Change Among the Elderly: A Nationwide Study in Finland, 2000-2020.

The incidence of inflammatory bowel disease [IBD] is stabilising in many Western countries. Some still show increasing incidence. Our objective was to determine the latest trends in IBD incidence and prevalence in Finland and to compare these among different age groups and between different geographical areas. We used the nationwide registry of the Social Insurance Institute of Finland to identify new IBD cases during the period 2000-2020. Crude, age-specific, and age-standardised incidence rates were calculated. Prevalence was estimated using valid reimbursements from the same database in 2000-2020. We identified 42 498 new IBD cases. The crude annual incidence increased in ulcerative colitis [UC] from 20 to 35 (incidence date ratio [IRR] 1.03, 95% confidence interval [CI] 1.02-1.03), in Crohn's disease [CD] from 8 to 13 [IRR 1.02, CI 1.02-1.03] and in IBD overall from 28 to 48 per 100 000 person-years [IRR 1.02, CI 1.02-1.03]. Men had higher incidence than women in UC, but in CD the incidences were equal. The incidence of IBD increased in all age groups except for small children. The increase in both UC and CD was most marked among the elderly aged over 70. A north-south gradient was discernible. The crude prevalence of IBD increased from 376 to 972 per 100 000 (prevalence rate ratio [PRR] 1.05, CI 1.05-1.05). The incidence of IBD, UC, and CD is increasing in Finland. The increase is most notable in the elderly. Current prevalence of IBD is 1%.

Differential diagnosis of Crohn’s disease and intestinal tuberculosis: development and assessment of a nomogram prediction model

BackgroundChina is a region with a high incidence of tuberculosis, and the incidence of IBD has also been rising rapidly in recent years. Differentiating Crohn’s disease(CD) from intestinal tuberculosis (ITB) has become a very challenging issue. We aimed to develop and assess a diagnostic nomogram to differentiate between CD and ITB to improve the accuracy and practicability of the model.MethodsA total of 133 patients (CD 90 and ITB 43) were analyzed retrospectively. Univariate and multivariate logistic regression analysis was included to determine the independent predictive factors and establish the regression equation. On this basis, the nomogram prediction model was constructed. The discrimination, calibration and clinical efficiency of the nomogram were assessed using area under the curve(AUC), C-index, calibration curve, decision curve analysis (DCA) and clinical impact curve.ResultsT-SPOT positive, cobblestone appearance, comb sign and granuloma were significant predictors in differentiating CD from ITB. Base on the above independent predictors, a diagnostic nomogram was successfully established. The sensitivity, specificity, accuracy of the prediction model are 94.4%, 93.0%, 94.0% respectively. The AUC and the C-index of the prediction model are both 0.988, which suggest that the model had a good discrimination power. The calibration curve indicated a high calibration degree of the prediction model. The DCA and clinical impact curve indicated a good clinical efficiency of the prediction model which could bring clinical benefits.ConclusionA nomogram prediction model for distinguishing CD from ITB was developed and assessed, with high discrimination, calibration and clinical efficiency. It can be used as an accurate and convenient diagnostic tool to distinguish CD from ITB, facilitating clinical decision-making.

Incidence, Management, and Outcomes of Very Early Onset Inflammatory Bowel Diseases and Infantile-Onset Disease: An Epi-IIRN Study

In this nationwide study from the Israeli Inflammatory Bowel Disease Research Nucleus, we aimed to describe the incidence of very early onset inflammatory bowel diseases (VEOIBDs) with a focus on infantile-onset disease and to compare management and disease course with older children. Data were retrieved from the 4 Israeli Health Maintenance Organizations covering 98% of the population. Pediatric-onset IBD was categorized as follows: adolescent onset (10 to <18 y), early onset (6 to <10 y), VEOIBD (0 to <6 y), toddler onset (2 to <6 y), and infantile onset (<2 y). A total of 5243 children with 35,469 person-years of follow-up evaluation, were diagnosed with IBD during 2005 to 2020: 4444 (85%) with adolescent onset, 548 (10%) with early onset, and 251 (4.8%) with VEOIBD, of whom 81 (1.5%) had infantile onset. The incidence of pediatric-onset IBD increased from 10.8 per 100,000 in 2005 to 15.3 per 100,000 in 2019 (average annual percentage change, 2.8%; 95% CI, 2.2%-3.4%), but that of VEOIBD remained stable (average annual percentage change, 0%; 95% CI, -2.5% to 2.6%). The infantile-onset and toddler-onset groups were treated less often with biologics (36% and 35%, respectively) vs the early onset (57%) and adolescent-onset groups (53%; P < .001). The time to steroid dependency was shorter in infantile-onset (hazard ratio [HR], 2.1; 95% CI, 1.5-2.9) and toddler-onset disease (HR, 1.6; 95% CI, 1.2-2.0) vs early onset and adolescent-onset disease, but time to hospitalizations, time to surgery, and growth delay were worse only in infantile-onset disease. In a multivariable model, infantile-onset patients had a higher risk for surgery (HR, 1.4; 95% CI, 1.1-1.9) and hospitalization (HR, 1.7; 95% CI, 1.2-2.4) than the toddler-onset group. The incidence of VEOIBD remained stable. Infantile-onset IBD had worse outcomes than older children, while toddler onset had mostly similar outcomes, despite less frequent use of biologics.

Intake of ultra-processed foods is associated with an increased risk of Crohn's disease: a cross-sectional and prospective analysis of 187,154 participants in the UK Biobank.

Ultra-processed food (UPF) consumption has been linked to globally increasing incidence and prevalence in chronic diseases including inflammatory bowel diseases (IBD). We aimed to investigate the association between UPF consumption and IBD incidence, prevalence, and IBD-relevant outcomes. We performed a cross-sectional and prospective cohort study in 187,854 individuals included in the national UK Biobank using 24-hour dietary recall questionnaires. Multivariable logistic regression and Cox proportional hazard regression were used to examine the association between UPFs and the prevalent, and incidence risk of IBD, respectively. 185,849 participants with a mean age of 56.2 were included with a mean follow-up of 9.84 years. During follow-up, 841 developed IBD (251 Crohn's disease (CD), and 590 ulcerative colitis (UC)). UPF intake in IBD patients was significantly higher (CD: OR 1.94 (95%CI: 1.52 - 2.49, p<0.001); UC: OR 1.39 (95%CI: 1.17 - 1.65, p<0.001)). Compared to low consumption, higher UPF consumption was significantly associated with incident CD (HR 2.00 (95%CI: 1.32 - 3.03, p=0.001), but not UC. We also found a significant association between UPF intake and need of IBD-related surgery (HR 4.06 (95%CI: 1.52 - 10.86, p= 0.005)). Higher intake of UPFs was associated with higher incidence of CD, but not UC. In individuals with a pre-existing diagnosis of IBD, consumption of UPFs was significantly higher compared to controls, and was associated with an increased need for IBD-related surgery. Further studies are needed to address the impact of UPF intake on disease pathogenesis, and outcomes.

Metabolic dysfunction-associated fatty liver disease and liver function markers are associated with Crohn’s disease but not Ulcerative Colitis: a prospective cohort study

BackgroundMetabolic dysfunction-associated fatty liver disease (MAFLD) is recently recognized as a condition featured with metabolic dysfunctions in liver. It has been supposed that MAFLD might contribute to the development of IBD, but evidence from prospective cohort studies is lacking and inconclusive.MethodsA total of 221,546 females and 183,867 males from the UK Biobank cohort enrolled in 2006–2010 were included to examine whether MAFLD and liver function markers were related to incident IBD. MAFLD was identified based on hepatic steatosis defined by fatty liver index plus the prevalence of overweight, type 2 diabetes mellitus, or at least two metabolic abnormalities. Biomarker related to liver function (albumin [ALB], alkaline phosphatase [ALP], alanine transaminase [ALT], aspartate transaminase [AST]; gamma-glutamyl transferase [GGT], total bilirubin [TB], total protein [TP]) was measured using colorimetric or enzymatic assays. The incidence of IBD was ascertained based on primary care and inpatient records. Cox proportional hazard model was used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for the magnitude of their associations.ResultsWith a mean follow-up of 12.1 years, 2228 incident IBD cases were documented. We identified 150,385 individuals with MAFLD at baseline and 86% participants’ circulating liver function markers were within the normal range. Participants with MAFLD were associated with a 12% (HR 1.12, 95% CI 1.03, 1.23, p = 0.012) increased risk of IBD compared with those without MAFLD at baseline; the association was stronger (p-Heterogeneity = 0.006) with Crohn's disease (HR 1.35, 95% CI 1.15, 1.59, p < 0.001) than ulcerative colitis (HR 1.03, 95% CI 0.93, 1.15, p = 0.57). As for the serum liver function markers, the HRs of IBD for per 1-SD increment in ALB, ALP, AST, and TB concentration were 0.86 (95% CI 0.83, 0.90, p < 0.001), 1.18 (95% CI 1.13, 1.24, p < 0.001), 0.95 (95% CI 0.91, 0.99, p = 0.027), 0.92 (95% CI 0.87, 0.96, p < 0.001), respectively. We did not observe significant associations of GGT and TP with IBD.ConclusionsIndividuals with MAFLD were at increased risk of developing IBD, especially CD, but not UC. Circulating levels of liver function biomarkers as the surrogate indicators of MAFLD were also associated with IBD risk.

Glycerol monolaurate ameliorates DSS-induced acute colitis by inhibiting infiltration of Th17, neutrophils, macrophages and altering the gut microbiota.

Background and aimsInflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear.MethodsAcute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg−1) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation.ResultsGML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1β and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-β). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus.ConclusionsWe showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.

FRI293 - Circulating miR-21 parallels the incidence of IBD in PSC patients

FRI293 - Circulating miR-21 parallels the incidence of IBD in PSC patients

Increased number of children in households may protect against inflammatory bowel disease.

The increasing incidence of inflammatory bowel disease (IBD: Crohn's disease and ulcerative colitis) around the world has coincided with a wide array of environmental and epidemiologic changes. The relationship between IBD incidence and household or family size decline, however, has not been examined before. Our background epidemiological analyses suggested an inverse association between household size and IBD incidence. We aimed to examine this further in a murine model. We designed a unique two-generation cohousing model of family size and IBD susceptibility in C57BL/6J mice. Serial fecal microbiomes during cohousing were examined by high-throughput 16S rRNA sequencing. After cohousing for 10 days, mice were exposed to dextran sulfate sodium (DSS) to induce acute colitis. Body weight as a significant correlate of colitis severity was measured. Mice in a large household arrangement demonstrated less weight loss than mice in the small household arrangement in the DSS model. Age- and housing-dependent microbiome shifts were found. Larger households may be protective against intestinal inflammation through intergenerational microbiome modulation. Our observations may set the foundation for age-dependent, microbiome-directed future prevention against IBD. Epidemiological analyses in this study suggested that IBD incidence may inversely correlate with household size (an indicator of family size/children per family), which has not been examined before. A uniquely designed two-generation cohousing model of family size and IBD susceptibility in mice supported our epidemiologic observations. Microbiome changes in our cohousing model may set the foundation for age-dependent, microbiome-directed prevention against IBD.

Food as Treatment of Inflammatory Bowel Diseases.

ABSTRACTInflammatory bowel diseases (IBD), namely, Crohn’s disease (CD) and ulcerative colitis (UC), are lifelong and incurable chronic inflammatory diseases affecting 6.8 million people worldwide. By 2030, the prevalence of IBD is estimated to reach 1% of the population in Western countries, and thus there is an urgent need to develop effective therapies to reduce the burden of this disease. Microbiome dysbiosis is at the heart of the IBD pathophysiology, and current research and development efforts for IBD treatments have been focused on gut microbiome regulation. Diet can shape the intestinal microbiome. Diet is also preferred over medication, is safe, and has been proven to be an effective strategy for the management of IBD. Therefore, although often overlooked, dietary interventions targeting the microbiome represent ideal treatments for IBD. Here, I summarize the latest research on diet as a treatment for IBD from infancy to adulthood, compile evidence of the mechanisms of action behind diet as treatment, and, lastly, provide insights into future research focusing on culturally tailored diets for ethnic minority groups with increased incidence of IBD yet underrepresented in nutrition research.

Pre- and Perinatal Factors Predicting Inflammatory Bowel Disease: A Population-Based Study with Fifty Years of Follow-Up.

Pre- and perinatal events may be associated with an increased risk of inflammatory bowel disease [IBD]. We aimed to investigate the role of pre- and perinatal factors as potential risk factors for the development of IBD in a population with a follow-up of 50years. We conducted a nested case-control study, reporting IBD incidence among individuals born in 1964-76, for whom pre- and perinatal exposures were reported as part of the Jerusalem Perinatal Study [JPS], by linking them to the database of the epidemiology group of the Israeli IBD Research Nucleus [epi-IIRN], including all IBD patients in Israel since 2005 and their matched controls. We identified 2789 individuals within the epi-IIRN cohort who were also included in the JPS cohort [n=90079]: 746 IBD patients (405 with Crohn's disease [CD] and 341 with ulcerative colitis [UC]) and 2043 non-IBD controls. Those with a 'Non-western' family origin had decreased odds of developing CD and UC. High socioeconomic status was associated with CD but not UC. Low birth weight [≤2500g] occurred less frequently in IBD cases compared to controls, especially in UC patients, showing a protective effect. Being the first born was associated with CD, and having older siblings lowered the odds of developing CD, decreasing 7% with each additional sibling. Smoking and breastfeeding data were available for a subset of individuals, but neither was associated with IBD development. This population-based study identifies several pre- and perinatal variables as predictors of IBD development. This information may be helpful to facilitate implementation of early diagnosis interventions and family follow-up protocols.

A4 HELMINTH-DERIVED METABOLITES INDUCE A TOLEROGENIC PROFILE IN DENDRITIC CELLS AND ALLEVIATE EXPERIMENTAL COLITIS

BackgroundInflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by abdominal pain, bloody diarrhea, fatigue, weight loss, and diminished quality of life. The morbidity associated with IBD is a result of loss of tolerance towards the gastrointestinal commensal microbiota. The high incidence of IBD in Western societies is inversely correlated with the low incidence of intestinal helminth parasite infections, potentially due to the ability of the helminth parasite to induce tolerance by inducing tolerogenic dendritic cells (tolDC) polarization. Although macromolecules from helminth such as proteins and polysaccharides have been shown to polarize tolDCs, to characterize a novel pathway, in this study we focused on small molecules such as metabolites in the helminth secretome. We hypothesized that helminth-derived metabolites (HDMs) polarize DCs towards a tolerogenic phenotype, which alleviates colitis.AimsTo evaluate and characterize the tolerogenic response induced by HDMs in DCs, and its ability to alleviate colitis.Methods Heligmosomoides polygyrus worms were culture for 24 h and HDMs were isolated from conditioned media by chromatography. Bone marrow dendritic cells (BMDCs) were differentiated with GM-CSF for 8 days and then incubated with HDM for 4 h before LPS stimulation for 20 h. Cytokine secretion was measured by ELISA. The transcriptome of DCs treated with HDMs was assessed by RNAseq. Colitis was induced by giving 3% DSS in drinking water for 5 days followed by 3 days of tap water. The anti-colitic effect of HDMs was assessed by daily treatment with HDM or DCs treated with HDM in the 3 days of tap water.ResultsPre-treatment with HDM decreased LPS-induced TNF and increased IL-10 release by BMDCs, compared to control BMDCs. Colitic mice treated with HDM presented lower disease activity scores, less colon shortening, decreased weight loss, and healthier histopathology compared to vehicle-treated colitic mice. Importantly, there was an increased frequency of CD11c+ CD103+ DCs in the colon of HDM-treated mice, suggesting that HDM alleviates colitis by increasing the abundance of tolDCs in the colon. Adoptive transfer of HDM-treated DCs also reduced the severity of colitis compared with vehicle-treated mice or mice that received naïve DCs. These results indicate that HDM induced tolerogenic DCs, which in turn ameliorates DSS colitis. RNAseq showed that HDM upregulated 183 and downregulated 76 genes. These differentially expressed genes may indicate a novel mechanism by which helminths induce a tolerogenic profile in DCs.ConclusionsHDMs induce tolerogenic DCs and alleviate DSS-induced colitis.Funding AgenciesNSERC and FRQNT

A195 GEOEPIDEMIOLOGICAL CHANGES DUE TO ALTERATIONS IN DIAGNOSTIC ROME CRITERIA FOR IRRITABLE BOWEL SYNDROME

Abstract Background Irritable bowel syndrome (IBS) is a positive diagnosis based on consensus opinions. The Rome (R) criteria, have gone through 4 rounds. R4 restricted diagnosis of IBS over R3, reducing global prevalence. Previously, there were no correlations of world distributions of IBS and Inflammatory Bowel Disease [IBD](Lovell). There are also epidemiological studies showing relationships between IBD and national wealth. Aims We reevaluate relationships among different R criteria and latitude(Lat), lactose digestion status (LNP), human development index(HDI), gross domestic product/capita(GDP/c), Crohn’s disease (CD and ulcerative colitis (UC) incidence(i) and prevalence(p). Methods Literature on world prevalence of national IBS (Oka,Sperber), IBD rates (Ng), and GDP (Lopez Ruiz) (4) were sought on PubMed and Google Scholar.National HDI(08 or 2016) were available on the internet (http://hdr.undp.org/en/data). National lactase distributions and latitudes were quoted (Szilagyi). Target dates were for the year 2008±8yrs. After log transformation of IBD incidence, Pearson’s correlations were carried out.(strong at; r ≥0.7, moderate ≥0.5, weak ≤ 0.49, negligible ≤ 0.3). (significance was p&amp;lt;0.05). Results Correlations of HDI08 and HDI16 was 0.98. Comparisons of R2 and a composite based on Manning, R 1 and 2 (Lovell) was r = 0.96 (N21 countries), Correlation of R 3 and 4 were r = 0.85 (N17). Correlations of R2 and R3 or R4 were negligible (r = -0.2 (n15) and -0.12 (N22). Correlations of R2 and both economic metrics were weak but significant (r = 0.42 – r = 0.49, p &amp;lt; 0.03 - &amp;lt; 0.001). However, correlations of metrics with R3 were non significant and negligible with R4. Comparisons of R2 with LNP or Lat were negligible, but those of R3 or R4 with Lat were significant. Comparisons of R3 with CDp showed a strong correlation while R4 showed a weak but significant correlation with UCi. R2 had negligible correlations with IBD. Conclusions Although, these results are based on limited data variations in R criteria have changed relations with IBS prevalence.Earlier R criteria showed increased IBS in poorer nations. The recent R3 and R4 criteria are independent of national economy, but show more relations with increasing latitudes. Consequences of the change include R3 and 4 reflecting western society symptoms perhaps linking it more with IBD.It is unclear if this new relationship incorporates an irritable inflammatory bowel syndrome (Gajula).The generalizability therefore of the new R4 criteria may still be limited. Table: Rome criteria compared to variables. Statistical significance * &amp;lt; 0.03, ** ≤ 0.05 Funding Agencies None

P690 Rates of IBD in New Zealand Māori population at Lakes District Health Board: low but increasing

Abstract Background Inflammatory bowel disease (IBD) is a chronic, inflammatory disease that is increasingly prevalent in New Zealand (NZ). Previous regional studies describe significantly lower rates of IBD in Māori (the indigenous people of NZ) compared to non-Māori. We aimed to describe IBD incidence and prevalence at Lakes District Health Board (DHB), with a focus on the Māori population. Methods All patients with IBD at Lakes DHB are managed using an IBD database. The database was reviewed and demographic, clinical, IBD phenotype, treatment and surgical data were extracted. Rates of IBD and other characteristics were compared between Māori and non-Māori. Results 197 IBD patients were identified, consisting of 100 (51%) with Crohn’s disease, 77 (39%) with ulcerative colitis, and 20 with IBD-unspecified. The median age was 48±17 and 100 (50.8%) were males. 15 (7.6%) patients were Māori and 182 (92.4%) European/other (Figure 1), leading to IBD ethnic-specific prevalences of 34.9 and 256.8/100,000, respectively. Rates of current/ex-smoking were similar in Māori and non-Māori (~30%), so was biologic use (40%). Despite statistically insignificant, Māori were more likely to be hospitalised over the last ten years (mean admissions 1.8 vs 1.1). In the last 20 years, there has been a steady increase in IBD incidence among non-Maori population. In Māori population, although the rates were consistently lower, more were diagnosed over the last 5 years, demonstrating an increasing incidence (Figure 2). Figure 1. Lakes DHB demographics and IBD status Figure 2. Comparison of IBD incidence in Māori and non-Māori at Lakes DHB Conclusion Our findings are concordant with previous studies showing gradually increased rates of IBD in NZ and low rates in Māori. However, rates in the last five years are increasing in Māori population which may reflect a true increase in incidence due to changes in environmental risk factor exposure or increased rates of presentation and diagnosis in Māori over the last five years.

P085 Paneth cells translate dietary lipid exposure into gut inflammation

Abstract Background Dietary constituents impact the development and course of IBD (1). Especially a Western style diet is associated with an increased incidence and prevalence of IBD (2). The role of polyunsaturated fatty acids (PUFA) in the development of IBD is broadly discussed. Recently we could show that PUFAs elicit a pro-inflammatory response in intestinal epithelial cells (IEC) in a Glutathione peroxidase 4 (GPX4) deficient setting, which resembled phenotypic hallmarks of human CD (3). GPX4, an anti-oxidative enzyme, was described to be a risk gene for the development of CD (4) and is deficient in IECs derived from inflamed areas of the small intestine of CD patients (3). Stress responses in Paneth cells (PC) trigger small intestinal gut inflammation (5). In this study, we describe PC as originators of GPX4-restricted and PUFA-induced intestinal inflammation. Methods We analyzed PC morphology in mice lacking one allele of GPX4 specifically in IECs (GPX4+/-IEC) by electron microscopy. We generated mice lacking both alleles of Gpx4 specifically in PC (GPX4ΔPC) and exposed these mice (and wildtype controls) to a Western diet enriched with PUFAs for 12 weeks. Intestinal inflammation was assessed by histology and immunohistochemistry. Further we analyzed small intestinal whole tissue cultures and evaluated cytokine production by ELISA. Results Paneth cells of mice lacking one allele of Gpx4 showed morphological signs of ER-stress at baseline and after exposure to a PUFA-WD for 12 weeks when compared to WT mice (Fig 1a). Based on these results, we dissected a role for PC in GPX4-restricted gut inflammation. When fed a PUFA WD for 12 weeks GPX4ΔPC mice developed a CD like enteritis while WT controls did not (Fig 1b). A WD did not induce this inflammatory response in GPX4ΔPC or WT mice. The infiltrating leukocytes contained mainly neutrophils and macrophages (indicated by positive F4/80 staining, Fib 1c). Whole tissue cultures derived from GPX4ΔPC mice fed a PUFA WD produced more Interleukin-6 and CXCL-1, the murine homologue of the human Interleukin-8, compared to whole tissue cultures derived from WT mice fed the same diet (Fig 2). Figure legend 1a) % of PC showing massive, medium or no ER dilatation 1b&amp;c) enteritis score and representative H&amp;E and F4/80 staining 2) IL-6 and CXCL-1 in supernatant of whole tissue jejunal samples Conclusion The presented data identify Paneth cells to be crucially involved in the development of PUFA induced enteritis in genetically susceptible hosts.