Risk Of Crohn's Disease Research Articles

GWAS-associated bacteria and their metabolites appear to be causally related to the development of inflammatory bowel disease.

Accumulating evidence has suggested that the imbalance of gut microbiota is commonly observed in patients with inflammatory bowel disease (IBD). However, it remains unclear whether dysbiosis is a cause or consequence of chronic intestinal inflammation. We aimed to investigate the causal relationships of gut microbiota and metabolites with IBD, including ulcerative colitis (UC) and Crohn's disease (CD). We applied two-sample Mendelian randomization using summary statistics from the gut microbiota genetic consortium (n = 1812), the Framingham Heart Study (n = 2076) and the International IBD Genetics Consortium (n = 86,640). Using the genetic approach, the increase in OTU10032 unclassified Enterobacteriaceae was associated with higher risks of IBD (OR, 1.03; 95% CI, 1.00-1.06; P = 0.033) and CD (1.04; 1.01-1.08; P = 0.015). Importantly, an Enterobacteriaceae-related metabolite taurine was positively associated with risks of IBD (1.04; 1.01-1.08; P = 0.016) and UC (1.05; 1.01-1.10; P = 0.024). Notably, we also found betaine, a downstream product of Enterobacteriaceae metabolism, was causally associated with a higher risk of CD (1.10; 1.02-1.18; P = 0.008). In addition, increased Erysipelotrichaceae family were causally related to lower risks of IBD (0.88; 0.78-0.98; P = 0.026) and UC (0.86; 0.75-0.99; P = 0.042), and Actinobacteria class (0.80; 0.65-0.98; P = 0.028) and Unclassified Erysipelotrichaceae (0.79; 0.64-0.98; P = 0.036) were associated with lower risks of UC and CD, respectively. Our finding provided new insights into the key role of gut metabolites such as taurine and betaine in host-microbiota interactions of IBD pathogenesis, indicating that host-microbe balance strongly influences inflammatory conditions.

Risk Factors for Incident Inflammatory Bowel Disease According to Disease Phenotype

We examined whether relationships between known risk factors for Crohn's disease (CD) and ulcerative colitis (UC) differ according to disease phenotype, defined by Montreal classification, at the time of diagnosis. We performed a prospective cohort study of 208,070 adults from the Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS). Dietary, lifestyle, and medical data were obtained at baseline and every 2-4 years. We confirmed cases of inflammatory bowel disease (IBD) and their phenotypes via medical record review. We tested for heterogeneity across CD subtypes using the likelihood ratio test and for linear heterogeneity across UC subtypes using the meta-regression method. We ascertained 346 cases of CD and 456 cases of UC over 5,117,021 person-years of follow-up (1986-2016 for NHS and HPFS; 1991-2017 for NHSII). Fiber intake was associated with decreased risk for ileocolonic but not ileal or colonic CD (Pheterogeneity= .04). Physical activity was associated with decreased risk of nonstricturing and nonpenetrating CD but not of penetrating CD (Pheterogeneity= .02). Higher body mass index and current smoking were associated with decreased risk of proctitis and left-sided UC but not of pan-UC (Plinear heterogeneity= .004 and .02, respectively). The associations between other risk factors examined and risk of CD and UC did not differ by disease phenotype (all Pheterogeneity > .06). In 3 large prospective cohorts, we observed that dietary and lifestyle risk factors for IBD may differ according to disease phenotype. These findings highlight the need for disease stratification in future epidemiologic studies.

Single-Cell Analysis Reveals Unexpected Cellular Changes and Transposon Expression Signatures in the Colonic Epithelium of Treatment-Naïve Adult Crohn's Disease Patients.

Background & AimsThe intestinal barrier comprises a monolayer of specialized intestinal epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter intestinal permeability in a genetically susceptible host, resulting in a chronic and debilitating condition known as Crohn’s disease (CD). Defining the molecular changes in each IEC type in CD will contribute to an improved understanding of the pathogenic processes and the identification of cell type–specific therapeutic targets. We performed, at single-cell resolution, a direct comparison of the colonic epithelial cellular and molecular landscape between treatment-naïve adult CD and non–inflammatory bowel disease control patients.MethodsColonic epithelial-enriched, single-cell sequencing from treatment-naïve adult CD and non–inflammatory bowel disease patients was investigated to identify disease-induced differences in IEC types.ResultsOur analysis showed that in CD patients there is a significant skew in the colonic epithelial cellular distribution away from canonical LGR5+ stem cells, located at the crypt bottom, and toward one specific subtype of mature colonocytes, located at the crypt top. Further analysis showed unique changes to gene expression programs in every major cell type, including a previously undescribed suppression in CD of most enteroendocrine driver genes as well as L-cell markers including GCG. We also dissect an incompletely understood SPIB+ cell cluster, revealing at least 4 subclusters that likely represent different stages of a maturational trajectory. One of these SPIB+ subclusters expresses crypt-top colonocyte markers and is up-regulated significantly in CD, whereas another subcluster strongly expresses and stains positive for lysozyme (albeit no other canonical Paneth cell marker), which surprisingly is greatly reduced in expression in CD. In addition, we also discovered transposable element markers of colonic epithelial cell types as well as transposable element families that are altered significantly in CD in a cell type–specific manner. Finally, through integration with data from genome-wide association studies, we show that genes implicated in CD risk show heretofore unknown cell type–specific patterns of aberrant expression in CD, providing unprecedented insight into the potential biological functions of these genes.ConclusionsSingle-cell analysis shows a number of unexpected cellular and molecular features, including transposable element expression signatures, in the colonic epithelium of treatment-naïve adult CD.

Association between ABO blood group and risk of Crohn's disease: A case-control study in the Chinese Han population.

BackgroundBlood group O has been reported to be a potentially protective factor for Crohn's disease (CD) susceptibility in Caucasian and Korean populations, but a similar conclusion was not found in a Chinese study. The present study investigated the potential association in the Chinese Han population.MethodsWe included 275 CD patients, 132 ulcerative colitis (UC) patients and 1201 healthy individuals in this case‐control study. The demographic characteristics and ABO blood group were compared among the three groups. The clinical characteristics and treatment of CD were further investigated according to the blood group distribution.ResultsThe blood group distribution in CD patients was significantly different from healthy controls, and the frequency of O blood in CD patients was significantly lower compared to healthy controls. After adjusting for age and gender, the non‐O blood groups remained significantly associated with CD susceptibility in propensity score‐adjusted and propensity score‐matched analyses. Compared to CD patients with non‐O blood groups, patients with O blood were at a lower risk of developing penetrating disease, more likely to receive immunosuppressant treatment and less likely to receive biological treatment.ConclusionOur results confirmed that non‐O blood groups were significantly associated with an increased risk of CD in the Chinese Han population.

Genetic variants involved in innate immunity modulate the risk of inflammatory bowel diseases in an understudied Malaysian population.

Inflammatory bowel diseases (IBD) are chronic gastrointestinal inflammatory conditions comprising two major subtypes: Crohn's disease (CD) and ulcerative colitis (UC). The incidence of IBD is increasing in Asian countries including Malaysia. The aim of this study was to determine whether 32 single nucleotide polymorphisms (SNPs) strongly associated with IBD from genome-wide association studies, performed mainly in Caucasian populations, are associated with IBD in a Malaysian population, correlating these findings with local and systemic inflammation. Selected SNPs were investigated in a Malaysian cohort comprising 36 IBD patients and 75 controls using customized matrix-assisted laser desorption ionization time-of-flight genotyping. Local mRNA and/or systemic protein levels of IL-10, IL-12, IL-22, IL-23, and TNF-α were measured in these same subjects. ATG16L2 rs11235667 and LINC00824 rs6651252 was significantly associated with increased CD risk while IL12B rs56167332 was a significant protective factor. Three SNPs (SBNO2 rs2024092, CARD9 rs10781499, and rs17085007 between GPR12-USP12) were significantly associated with increased UC risk while NKX2-3 rs4409764 was a significant protective factor. After adjusting for age, gender, and ethnicity, SBNO2 rs2024092, ATG16L2 rs11235667, CARD9 rs10781499, and LINC00824 rs6651252 remained associated with IBD. Interestingly, the risk alleles of IL10 rs3024505, CARD9 rs1078149, and IL12 rs6556412 were associated with higher levels of IL-10, IL-22, and IL-23 in these same subjects, respectively. This study identified eight SNPs associated with IBD and/or its subtypes in the Malaysia population, significantly advancing our understanding of the genetic contribution to IBD in this understudied population. Three of these SNPs modulated relevant cytokine levels and thus, may directly contribute to IBD pathogenesis.

Alcohol consumption and risk of inflammatory bowel disease among three prospective US cohorts.

There are limited data on alcohol dose and types and risk of Crohn's Disease (CD) and Ulcerative Colitis (UC). We therefore sought to comprehensively examine the association between alcohol consumption and risk of CD and UC. We conducted a prospective cohort study of 237,835 participants from the Nurses' Health Study, Nurses' Health Study II, and Health Professional Follow-Up Study. Alcohol consumption was obtained through questionnaires submitted every four years; additional covariates were obtained at two or four-year intervals. Cases were confirmed independently by two physicians through medical record review. We used Cox proportional hazards regression to estimate age and multivariable-adjusted hazards ratios and 95% confidence intervals. Across 5,170,474 person-years of follow-up, 370 cases of CD and 486 cases of UC were documented. Increased consumption of alcohol intake was not associated with CD (Ptrend=0.455) or UC (Ptrend=0.745). Compared to non-users, the MV-adjusted HRs for 15.0+g/day of alcohol intake group were 0.84 (95% CI 0.56, 1.24) for CD and 1.08 (95% CI 0.77, 1.51) for UC. In analyses of alcohol subtypes, we observed that only moderate consumption of beer (>1-4 servings/week) was marginally associated with reduced risk of CD, while consumption of >4 servings/week of liquor was associated with an increased risk of UC. This prospective study did not identify a relationship between overall alcohol consumption and risk of CD or UC. Our suggestive associations between alcohol types and risk of CD and UC deserve additional investigation.

Occupational physical activity differentially affects the risk for developing later-onset Crohn’s disease and ulcerative colitis among middle-aged and older populations

Background A person’s occupation may increase his/her risk for developing inflammatory bowel disease (IBD). This study investigated the association between risk for later-onset of IBD and both specific occupations and occupational physical activity (OPA) levels. Materials and methods A multicenter hospital-based matched case-control study was conducted using the Inpatient Clinico-Occupational Survey database. Cases were patients with Crohn’s disease (CD) and ulcerative colitis (UC) patients admitted for the first time between 2005 and 2015. Four controls matched by age, sex, admission year and hospital were selected for each case. Cases and controls were grouped into the longest-held occupations as classified by the Japanese Standard Occupational Classification and OPA levels. We conducted conditional logistic regressions to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for IBD, CD and UC adjusted for alcohol consumption and smoking status. Results There were 564 cases (172 CD, 392 UC) and 2086 controls. The risk for UC was higher among sales workers and carrying, cleaning and packing workers (ORs 2.62 [95%CIs 1.18–5.82], 2.52 [1.04–6.09]). There was no association between occupation type and CD risk. Higher OPA level decreased CD risk (OR 0.51 [95%CIs 0.26–1.00]) and increased UC risk (OR 1.53 [95%CIs 1.02–2.30]). Conclusions Our study revealed that the risk for later-onset of UC, but not CD, was associated with longest-held 'service' and 'manufacture' work. The risk by OPA levels was inversely associated between CD and UC. Further studies are needed by follow-up method for long-term effects of physical activity.

Use of contraceptives and risk of inflammatory bowel disease: a nested case-control study.

SummaryBackgroundHow contraceptive formulation, dose, duration of therapy and mode of delivery affects the risk of inflammatory bowel disease (IBD) is poorly described.AimTo examine associations between types of hormonal contraception and development of IBD.MethodsThis was a nested case-control study using IQVIA Medical Research Data. Women aged 15-49 years with a new diagnosis of IBD were matched with up to six controls by age, practice and year. Odds ratios (OR) and 95% confidence intervals (95% CI) for incident IBD and use of contraception were calculated.Results4932 incident cases of IBD were matched to 29 340 controls. Use of combined oral contraceptive pills (COCPs) was associated with the development of Crohn's disease and ulcerative colitis (OR 1.60 [1.41-1.82] and 1.30 [1.15-1.45], respectively). Each additional month of COCP exposure per year of follow-up increased risk of Crohn's disease by 6.4% (5.1%-7.7%) and ulcerative colitis by 3.3% (2.1%-4.4%). Progestogen-only pills had no effect on Crohn's disease risk (OR 1.09 [0.84-1.40]) but there was a modest association with ulcerative colitis (OR 1.35 [1.12-1.64]). Parenteral contraception was not associated with the development of Crohn's disease or ulcerative colitis (OR 1.15 [0.99-1.47] and 1.17 [0.98-1.39], respectively).ConclusionsWe observed an increase in the risk of IBD with increasing duration of exposure to COCPs. Progestogen-only pills were not associated with Crohn's disease but there was a modest association with ulcerative colitis. There was no association between parenteral progestogen-only contraception and IBD. These findings are broadly consistent with a hypothesis that the oestrogen component of contraception may drive IBD pathogenesis.

Plasma concentrations of perfluoroalkyl substances and risk of inflammatory bowel diseases in women: A nested case control analysis in the Nurses’ Health Study cohorts

BackgroundPerfluoroalkyl substances (PFASs) are synthetic compounds used in a wide variety of industrial and consumer applications. An association between PFAS exposure and risk of ulcerative colitis (UC) has been reported in a highly exposed population. However, data are limited on risk of inflammatory bowel diseases (IBD) among individuals with background population levels of PFAS exposure. ObjectivesWe set out to examine the association between plasma PFAS concentrations and risk of IBD among women in two population-based, prospective cohort studies in which pre-diagnostic blood specimens were available. MethodsWe conducted a nested case-control study in the Nurses' Health Study and Nurses' Health Study II cohorts. We identified 73 participants with incident Crohn's disease (CD) and 80 participants with incident UC who had provided blood samples before diagnosis. Cases were matched 1:2 to IBD-free controls. Plasma concentrations of five major PFASs were measured by liquid chromatography and tandem mass spectrometry. We used conditional logistic models to estimated odds ratios for risk of IBD according to log10-transformed PFAS concentrations, adjusting for potential confounders. ResultsIn multivariable models, we observed inverse associations between plasma concentrations of three PFASs and risk of CD (all P ≤ 0.012 for a standard deviation increase in log10PFAS). The inverse association with CD was strongest for perfluorodecanoate, where, compared to the lowest tertile, the odds ratio (OR) for the highest tertile was 0.39 (95% confidence interval, 0.17–0.92). No associations were observed between PFAS concentrations and UC risk. DiscussionOur results do not support the hypothesis that elevated PFAS exposure is associated with higher risk of UC. Contrary to expectation, our data suggest that circulating concentrations of some PFASs may be inversely associated with CD development.

Whole-milk consumption decreases the risk of inflammatory bowel disease: a two-sample Mendelian randomization analysis

Objective: The impact of dairy fat on inflammatory bowel disease remained inconclusive. We aimed to compare the effects of whole-milk and skimmed-milk consumption on the risk of inflammatory bowel disease using a Mendelian randomization analysis. Methods: We conducted a genome-wide association study of the preference for whole versus skimmed milk using data for 20,200 whole-milk consumers and 67,847 skimmed-milk consumers from the UK Biobank. The lead single nucleotide polymorphisms in the associated loci were identified at the genome-wide significance level, and were further employed as instrumental variables for whole-milk preference. We conducted a two-sample Mendelian randomization analysis with whole-milk preference as the exposure and inflammatory bowel disease as the outcome. The pleiotropic effects and heterogeneity of the instrumental variables were estimated using Mendelian randomization-Egger regression and Cochran Q test, respectively. This study was conducted using the UKB resources under the application "53536" . The UK Biobank was approved by the North West Multi-center Research Ethics Committee, the National Information Governance Board for Health and Social Care in England and Wales, and the Community Health Index Advisory Group in Scotland. Results: The genome-wide association study identified five lead nucleotide polymorphisms associated with whole-milk preference. Mendelian randomization indicated that whole-milk preference significantly decreased the risk of inflammatory bowel disease ( β =-1.735, P =0.048). Of the two subtypes, whole-milk preference was associated with a lower risk of Crohn disease ( β =-2.549, P =0.032), but had no significant effect on the risk of ulcerative colitis ( β =-1.002, P =0.44). Conclusion: Consumption of whole-milk fat may protect against Crohn disease, compared with skimmed milk. This conclusion was based on causal inference in a cohort study, and further validation in randomized controlled trials is warranted.

Ultra-processed Foods and Risk of Crohn’s Disease and Ulcerative Colitis: A Prospective Cohort Study

The rising incidence of inflammatory bowel disease in regions undergoing Westernization has coincided with the increase in ultra-processed food (UPF) consumption over the past few decades. We aimed to examine the association between consumption of UPFs and the risk of Crohn's disease (CD) and ulcerative colitis (UC). We performed a prospective cohort study of 3 nationwide cohorts of health professionals in the United States-the Nurses' Health Study (1986-2014), the Nurses' Health Study II (1991-2017), and the Health Professionals Follow-up Study (1986-2012). We employed Cox proportional hazards models with adjustment for confounders to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for CD and UC according to self-reported consumption of UPFs. The study included 245,112 participants. Over 5,468,444 person-years of follow-up, we documented 369 incident cases of CD and 488 incident cases of UC. The median age at diagnosis was 56 years (range, 29-85 years). Compared with participants in the lowest quartile of simple updated UPF consumption, those in the highest quartile had a significantly increased risk of CD (HR, 1.70; 95% CI, 1.23-2.35; Ptrend= .0008). Among different UPF subgroups, ultra-processed breads and breakfast foods; frozen or shelf-stable ready-to-eat/heat meals; and sauces, cheeses, spreads, and gravies showed the strongest positive associations with CD risk (HR per 1 standard deviation increase in intake, 1.18 [95% CI, 1.07-1.29], 1.11 [95% CI, 1.01-1.22], and 1.14 [95% CI, 1.02-1.27], respectively). There was no consistent association between UPF intake and UC risk. Higher UPF intake was associated with an increased risk of incident CD. Further studies are needed to identify specific contributory dietary components.

Sustained Crohn’s Disease Remission with an Exclusive Elemental and Exclusion Diet: A Case Report

The incidence of inflammatory bowel diseases, such as Crohn’s disease (CD), is increasing worldwide. Despite several new therapeutics to treat CD, many patients fail to respond to their medications and inevitably face surgical resection. While genetics plays a role in CD, environmental factors are potential triggers. Recent research from the past few years suggest that pro-inflammatory foods are associated with an increased risk of CD. Some studies have shown the benefit of including exclusion diets, such as the specific carbohydrate diet (SCD) and exclusive elemental diets, to induce CD remission, but published data is limited. This case study explores how an exclusive elemental and exclusion diet helped induce clinical and biochemical remission and radiologic healing in a young adult male who had failed to achieve remission using standard medical treatment. C-reactive protein (CRP), fecal calprotectin, and magnetic resonance enterography (MRE) served as objective markers of inflammation in this study.

Systematic Review and Meta-Analysis: Risk of Hospitalization in Patients with Ulcerative Colitis and Crohn's Disease in Population-Based Cohort Studies.

Inflammatory bowel diseases (IBD) lead to high morbidity and unplanned healthcare utilization. We conducted a systematic review with meta-analysis to estimate the cumulative incidence of IBD-related (and all-cause) hospitalization in patients with ulcerative colitis (UC) and Crohn's disease (CD). Through a systematic review to September 3, 2019, we identified population-based inception cohort studies in patients with IBD that reported patient-level cumulative incidence of hospitalization at 1, 3 and 5 years after diagnosis. Hospitalization risk was pooled using random effects meta-analysis, and risk factors analyzed through mixed-effects meta-regression and qualitative synthesis. In patients with UC (6 cohorts), 1-, 3- and 5-year risk of UC-related hospitalization was 10.4% (95% CI 8.2-13.2), 17.0% (95% CI 14.0-20.4) and 21.5% (95% CI 18.0-25.4), respectively, with considerable heterogeneity. In patients with CD (6 cohorts), 1-, 3- and 5-year risk of CD-related hospitalization was 29.3% (95% CI 20.0-40.8), 38.5% (95% CI 26.8-51.7) and 44.3% (95% CI 32.7-56.5), respectively, with considerable heterogeneity. On meta-regression, steady decline in risk of hospitalization was observed in patients diagnosed in a more contemporary era. Younger age at onset (both UC and CD), extensive colitis (UC), ileal-dominant CD, perianal CD and penetrating and/or stricturing behavior (CD) and early need for corticosteroids and immunosuppressive therapy (both UC and CD) were associated with increased risk of hospitalization. Approximately one in five and one in two patients with UC and CD are hospitalized within 5years of diagnosis, respectively. Population health management strategies are required to mitigate unplanned healthcare utilization.

Antitumour necrosis factor therapy is associated with de novo Crohn's disease after ileal pouch-anal anastomosis.

Tumour necrosis factor inhibitors (TNFi) have revolutionized the management of moderate to severe ulcerative colitis (UC) since their approval for UC in 2005. However, many patients ultimately require surgery with ileal pouch-anal anastomosis (IPAA). Development of de novo Crohn's disease (CD) following IPAA is an increasingly common and devastating complication, sometimes progressing to pouch failure. The aim of this study was to evaluate the association of preoperative TNFi exposure and the development of de novo CD after IPAA. A prospective single-centre inflammatory bowel disease (IBD) registry was searched for consecutive patients with UC undergoing IPAA during a 25-year period ending July 2018. Patients with preoperative CD or IBD-unclassified were excluded. De novo CD was diagnosed upon endoscopic evidence of five or more mucosal ulcers proximal to the ileal pouch any time after surgery and/or pouch fistula occurring more than three months after ileostomy closure. The study cohort consisted of 400 patients with a median follow-up of 44.0 (IQR 11-113) months. Sixty-two (16%) patients developed de novo CD 28.0 (IQR 6-67) months following ileostomy closure. Survival analysis of TNFi era patients revealed a significant increase in de novo CD risk in those with preoperative TNFi exposure. Multivariable proportional hazards modelling revealed two independent predictors for de novo CD development: older age was protective (HR 0.89 per 5-year increase; P=0.009) and preoperative TNFi exposure was hazardous (HR 2.10; P=0.011). This prospective study is the first to suggest an association between preoperative TNFi exposure and the development of de novo CD.

Obesity is Associated With Increased Risk of Crohn’s disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies

It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I2= 0%) compared with normal BMI (18.5 to <25 kg/m2). Each 5 kg/m2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I2= 0%). Similarly, with each 5 kg/m2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I2= 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I2= 0%). No associations were observed between measures of obesity and risk of UC. In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.

Detection of mutations in NOD2/CARD15 gene in Arab patients with Crohn's disease.

Background:Mutations in NOD2/CARD15 gene have been linked to an increased risk of Crohn's disease (CD). The objective of this study is to determine NOD2/CARD15 gene mutations, and their association with the risk of CD in Arabs in Kuwait.Methods:Four NOD2 gene mutations, including Pro268Ser (SNP5), Arg702Trp (SNP8), Gly908Arg (SNP12), and Leu1007FsinsC (SNP13) were examined in Arab CD patients (n = 103) and control subjects (n = 100). The genomic DNA was isolated and used in polymerase chain reaction (PCR) with four sets of specific primers. The PCR-amplified DNA fragments were sequenced and analyzed for the NOD2 mutations. Logistic regression was used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI).Results:Of the four genotyped variants, the Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) variants were not informative in our study sample due to minor allele frequency of <1%. The Pro268Ser (SNP5) mutation was detected in 17 (16.5%) CD patients and 32 (32.0%) controls. The Gly908Arg (SNP12) mutation was observed in 24 (23.3%) patients and 10 (10.0%) controls. In the dominant genetic risk model (i.e. carrying at least one minor allele), CD patients compared to controls were less likely to carry either the “CT” or “TT” genotype of variant Pro268Ser (SNP5; aOR = 0.43, 95% CI: 0.22–0.84). In contrast, CD patients compared to controls were more likely to carry the homozygous for the minor allele or the heterozygous genotypes of variant Gly908Arg (SNP12; aOR = 2.67, 95% CI: 1.19–5.97).Conclusions:In this Arab population, carrying at least one copy of the minor allele of Gly908Arg (SNP12) mutation in NOD2 gene was associated with increased susceptibility to CD, while having the heterozygous or homozygous for the minor allele genotype of the Pro268Ser (SNP5) mutation provided protection against CD. Mutations in Arg702Trp (SNP8) and Leu1007FsinsC (SNP13) were not detected in this sample of the Arab population in Kuwait.

Inflammatory Potential of the Diet and Incidence of Crohn's Disease and Ulcerative Colitis in the EPIC-Spain Cohort.

Diet may influence the development of inflammatory bowel disease through the modulation of inflammation. We investigated whether the inflammatory potential of the diet is associated with the risk of Crohn’s disease (CD) and ulcerative colitis (UC) in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The study included 32,633 participants aged 29–69 years. The inflammatory potential of the diet was measured by using an inflammatory score of the diet (ISD) based on a baseline dietary history questionnaire. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 21 years (674,547 person-years) of follow-up, 32 and 57 participants developed CD and UC, respectively. In multivariable analysis, a one-standard deviation (SD) increment in the ISD (two-unit increase) was associated with a higher risk of CD (HR of 1.71; 95% CI: 1.05–2.80; p = 0.031). By contrast, ISD was not associated with UC (HR for one-SD increment of 0.89; 95% CI: 0.66–1.19; p = 0.436). Our results suggest that consuming a more pro-inflammatory diet may contribute to the risk of CD, supporting that a healthy diet might be beneficial in its prevention. Further, larger studies are needed to verify these findings.

Prebiotic fructans have greater impact on luminal microbiology and CD3+ T cells in healthy siblings than patients with Crohn's disease: A pilot study investigating the potential for primary prevention of inflammatory bowel disease

Siblings of people with Crohn's disease (CD) share aspects of the disease phenotype (raised faecal calprotectin, altered microbiota), which are markers of risk for their own development of CD. The aim was to determine whether supplementation with prebiotic oligofructose/inulin induces a prebiotic response and impacts the risk phenotype in CD patients and siblings. Patients with inactive CD (n=19, CD activity index <150) and 12 of their unaffected siblings (with calprotectin >50μg/g) ingested oligofructose/inulin (15g/day) for three weeks. Faecal microbiota (qPCR), intestinal permeability (lactulose-rhamnose test), blood T cells (flow-cytometry) and calprotectin (ELISA) were measured at baseline and follow-up. Following oligofructose/inulin, calprotectin did not significantly change in patients (baseline mean 537 SD 535μg/g; follow-up mean 974 SD 1318μg/g, p=0.08) or siblings (baseline mean 73 SD 90μg/g: follow up mean 58 SD 72μg/g, p=0.62). Faecal Bifidobacteria and Bifidobacterium longum increased in patients and siblings; Bifidobacterium adolescentis and Roseburia spp. increased only in siblings. Compared with patients, siblings had a greater magnitude change in Bifidobacteria (+14.6% vs+0.4%, p=0.028), B.adolescentis (+1.1% vs 0.0% p=0.006) and Roseburia spp. (+1.5% vs-0.1% p=0.004). Intestinal permeability decreased significantly in patients after oligofructose/inulin to a level that was similar to siblings. Blood T cell abundance reduced in siblings but not patients following oligofructose/inulin. Oligofructose/inulin supplementation did not significantly impact calprotectin, but the prebiotic effect was more marked in healthy siblings compared with patients with inactive CD and was associated with alterations in other CD risk markers. Future research should focus on dietary intervention, including with prebiotics, in the primary prevention of CD.

Gp130 Signaling in NOD2-Driven Crohn’s Disease: A Key Player in Fibrosis and a Novel Target for Refractory Patients

Gp130 Signaling in NOD2-Driven Crohn’s Disease: A Key Player in Fibrosis and a Novel Target for Refractory Patients

Does a High-inflammatory Diet Increase the Risk of Inflammatory Bowel Disease? Results From the Prospective Urban Rural Epidemiology (PURE) Study: A Prospective Cohort Study

The empirical dietary inflammatory pattern (EDIP) was developed using data from the Nurses’ Health Study. 1 Tabung F.K. et al. J Nutr. 2016; 146: 1560-1570 Crossref PubMed Scopus (151) Google Scholar It is the weighted sum of 18 food groups, of which 9 are proinflammatory and 9 are anti-inflammatory, with higher scores suggesting proinflammatory diets and lower scores suggesting anti-inflammatory diets. The EDIP score has previously been validated in several populations and is correlated with systemic inflammatory markers. 1 Tabung F.K. et al. J Nutr. 2016; 146: 1560-1570 Crossref PubMed Scopus (151) Google Scholar , 2 Tabung F.K. et al. J Nutr. 2017; 147: 1567-1577 Crossref PubMed Scopus (61) Google Scholar , 3 Tabung F.K. et al. J Nutr. 2018; 148: 771-780 Crossref PubMed Scopus (28) Google Scholar A recent study by Lo et al 4 Lo C.H. et al. Gastroenterology. 2020; 159: 873-883 Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar concluded that people with higher EDIPs had a higher risk of developing Crohn’s disease (CD). Specifically, those in the highest quartile of EDIP scores had a 51% higher risk of CD compared with those in the lowest quartile. However, no association was seen between EDIP scores and risk of ulcerative colitis (UC). It is important to independently validate dietary predictors of inflammatory bowel disease (IBD), and so we evaluated whether higher EDIP scores were associated with a higher risk of developing IBD, using the Prospective Urban Rural Epidemiology (PURE) cohort. 5 Dehghan M. et al. Lancet. 2018; 392: 2288-2297 Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar , 6 Miller V. et al. Lancet. 2017; 390: 2037-2049 Abstract Full Text Full Text PDF PubMed Scopus (289) Google Scholar , 7 Teo K. et al. JAMA. 2013; 309: 1613-1621 Crossref PubMed Scopus (224) Google Scholar