Risk Factors For Inflammatory Bowel Disease Research Articles

Association of Risk Factors and Inflammatory Bowel Disease: a Case Control Study in a Tertiary Level Hospital

The rising incidence of inflammatory bowel disease (IBD) in Bangladesh supports the importance of various risk factors in disease etiology. This case-control study aims to measure association of IBD among the patients who were exposed to various risk factors. The study was conducted in patients with IBD and a control group without IBD in the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh during the period of March 2016 to January 2018. Diagnosed IBD patients aged more than eighteen years admitted or visiting for follow up in the Department of Gastroenterology were selected as cases. Controls were selected from patient’s attendants other than IBD, where age and sex were matched with cases. Controls were non-relative to the cases in the same department, and free from any bowel symptoms. Data were collected by using pre-tested questionnaire and then analyzed. Total 164 participants were selected among them 82 cases and 82 controls. Among the cases, 38 patients were diagnosed as ulcerative colitis and 44 patients were diagnosed as Crohn’s disease. Study found that ulcerative colitis were associated with the following factors namely being smoker (OR 20.31; 95% CI 2.39-172), exposure to pets (OR 11.24; 95% CI 1.86-67.76), not drinking boiling water (OR 7.33; 95%CI 1.62-33.05), bathing in open water such as river and ponds (OR 5.04; 95% CI 1.04-24.40), walking bare footed in grounds and toilet (OR 10.49; 95% CI 2.08-52.78), taking street food (OR 5.17; 95% CI1.15-23.28) and soft drinks (OR 11.55; 95% CI 0.24-9.48), where high odds ratios (OR) were measures. On the other hand, crohn’s disease were associated with the factors of being smoker (OR 10.30; 95%CI 1.15-91.9), exposure to pets (OR 19.19; 95% CI 1.74-211), not drinking boiling water (OR 10.33; 95% CI 2.54-43.51), bathing in open water such as river and ponds (OR 6.48;95% CI 1.35-31.09), consuming unpasteurized milk (OR 8.50; 95% CI 1.71-42.10) and soft drinks (OR 42.74; 95% CI 5.56-328). This study determined the risk factors of IBD in the ground of childhood behavior, hygienic condition and dietary habit for the development of IBD. Bangladesh Med J. 2022 May; 51(2): 1-12

ATG16L1 rs2241880/T300A increases susceptibility to perianal Crohn's disease: An updated meta-analysis on inflammatory bowel disease risk and clinical outcomes.

ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis. To perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features. Literature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP ) and 95% CI were calculated under the random effects model. Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (ORP : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP : 1.21, 95% CI: 1.07-1.38, p-value: 0.003). ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary.

Therapeutic advancement in inflammatory bowel disease by incorporating plant-based diet.

Identification and recognition of the ubiquitous environmental factor are prerequisite for treatment and prevention of the disease. The biggest problem with current practice in inflammatory bowel disease (IBD) is the lack of a widely appreciated ubiquitous environmental factor for the disease. The incidence of IBD is associated with dietary transition from a traditional diet to the current (westernized) diet. Prospective cohort studies and case-control studies indicate that the current diet is a risk factor for IBD. The current diet tends to cause gut microbial dysbiosis resulting in a pro-inflammatory state. Therefore, we regard our current diet as this factor. Even nutritionally balanced meals are unable to suppress relapse, particularly in Crohn's disease (CD). Therefore, we developed a plant-based diet (PBD) (lacto-ovo-semi-vegetarian diet) to counter the current diet. By incorporating the PBD into practice, we achieved far better outcomes in both ulcerative colitis (UC) and CD in both the induction and quiescent phases compared to the current standard therapy. All patients were treated on an inpatient basis and provided with a PBD. CD is far more untenable than UC and is destined to follow a disabling course. Therefore, infliximab was indicated in all patients with CD, but only in severe cases with UC. This infliximab and PBD as first-line (IPF) therapy broke the barrier of primary nonresponders to biologics (around 30%): the remission rate was 96% (44/46) in CD and 76% (13/17) in severe UC. A PBD can induce remission without medication in approximately one-third of mild cases of UC. All patients were advised to adhere PBD after discharge. In CD, a relapse-free outcome was achieved in nearly a half of patients (52%) at 10-year follow-up without biologics or immunosuppressants. Cumulative relapse rates for 51 initial episode cases of UC (18 mild, 30 moderate, 3 severe) at 1 and 5 years were 14% and 27%, respectively. We believe our assertion that the current diet is the ubiquitous environmental factor underlying IBD is correct and a PBD is right diet for the disease.

Adiposity as a risk factor for inflammatory bowel disease and the mediating effect of metabolic and inflammatory status: Apopulation-based cohort study.

To examine whether general and abdominal adiposity was a risk factor for the new-onset of inflammatory bowel disease (IBD) and the potential mediating effect of metabolic and inflammation status. A total of 492,998 individuals free of IBD recruited from 2006 to 2010 in the UK Biobank were included in our study, with ongoing follow-up linking to the health-related outcome. Multivariable Cox regression models were used to evaluate the associations between general adiposity (body mass index) and abdominal adiposity (waist circumference) and the subsequent risk of IBD and its subtype. We also investigated the potential mediating effects of metabolic and inflammation status by carrying out exploratory mediation analyses. During a median follow-up of 12.5years, we documented 2954 incident IBD cases (915 Crohn's disease [CD] and 2039 ulcerative colitis). After adjustment for important confounders, body mass index (hazard ratio [HR] highest quintile [Q5] vs. lowest quintile [Q1]=1.18, 95% confidence interval [CI] 1.04-1.32; P-trend=0.006) and waist circumference (HR Q5 vs. Q1 =1.30, 95% CI 1.14-1.49; P-trend <0.001) showed a positive association with the risk of IBD. The associations were partially mediated by metabolic status (24%; 15%), C-reactive protein (36%; 19%) and inflammation score (82%; 46%). Adiposity bore a risk factor for incident IBD, whereas unhealthy metabolism, especially inflammation, seemed to be an important intermediate condition between the association. Our findings provide evidence for possible mechanisms relating adiposity to IBD from an epidemiological perspective, and experimental studies are needed for further demonstration.

Mucinous and Signet-Ring Cell Colonic Adenocarcinoma in Inflammatory Bowel Disease: A Case-Control Study.

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case-control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum.

Promoting early testing and appropriate referral to reduce diagnostic delay for children with suspected inflammatory bowel disease, a narrative review.

When a child with chronic gastrointestinal (GI) symptoms presents to a primary care physician or general paediatrician, the clinician is challenged with differentiating between functional or organic disease. When there is a high suspicion of inflammatory bowel disease (IBD), rapid referral to a paediatric gastroenterologist for assessment and treatment will help protect against the sequelae of a delayed diagnosis for a child. However, this must be balanced against the need for ensuring appropriate referrals and avoiding invasive diagnostic testing for those with non-organic aetiology. The objective of this narrative review was to present evidence on specific presenting symptoms, testing, and risk factors of paediatric IBD that may aid the identification of children requiring timely referral for specialist care, thereby reducing the chance of a delayed diagnosis. Literature databases (Medline, Embase) were searched using terms specific to the population studied, and topic specific terms relating to each section of the review. Year limits were set for 2010-2022. Included papers were limited to original research, with meta-analyses considered where of benefit. Children often present with non-specific GI symptoms that may be associated with a delayed diagnosis for those with subsequent IBD. Symptoms such as rectal bleeding or weight loss may indicate the need for rapid referral. However, non-specific symptoms necessitate testing strategies to differentiate between those with possible IBD and non-organic conditions. Definitive laboratory testing for IBD is not yet available. This review outlines those metrics that should be considered and monitored, then utilised to make a comprehensive referral to tertiary care for specialist paediatric gastroenterology review. Summaries are provided relating to presenting symptoms, extra-intestinal manifestations (EIMs), and alarm symptoms in order to highlight those reported most frequently. The diagnostic accuracy and importance of interpreting faecal calprotectin (FC) levels, in conjunction with additional measures, are also outlined. Diagnostic testing to effectively identify children with IBD without the need for endoscopy is not yet available. Primary care physicians and general paediatricians must, therefore, rely on interpreting a combination of symptoms, laboratory parameters, and risk factors to assess the need for specialist referral and diagnosis.

Oat beta-glucan reduces colitis by promoting autophagy flux in intestinal epithelial cells via EPHB6-TFEB axis.

Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract, mainly including Crohn's disease and ulcerative colitis. Epidemiological findings suggest that inadequate dietary fibers intake may be a risk factor for IBD. Oat beta-glucan is a type of fermentable dietary fiber and has been proved to reduce experimental colitis. However, the mechanism remains unclear. The aim of this study was to explore the role and possible mechanism of oat beta-glucan in reducing experimental colitis. We used a dextran sulfate sodium (DSS)-induced mice acute colitis model to explore the potential mechanism of oat beta-glucan in reducing experimental colitis. As a result, oat beta-glucan upregulated the expressions of Erythropoietin-producing hepatocyte receptor B6 (EPHB6) and transcription factor EB (TFEB), promoted autophagy flux and downregulated the expressions of interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in intestinal epithelial cells (IECs). The role of the EPHB6-TFEB axis was explored using a lipopolysaccharide-induced HT-29 cells inflammation model. The results revealed that EPHB6 regulated the expression of TFEB, and knockdown of EPHB6 decreased the protein level of TFEB. When EPHB6 or TFEB was knocked down, autophagy flux was inhibited, and the anti-inflammatory effect of sodium butyrate, a main metabolite of oat beta-glucan in the gut, was blocked. In summary, our findings demonstrated that oat beta-glucan reduced DSS-induced acute colitis in mice, promoted autophagy flux via EPHB6-TFEB axis and downregulated the expressions of IL-1β, IL-6 and TNF-α in IECs, and this effect may be mediated by butyrate.

Effect and mechanism of total ginsenosides repairing SDS‑induced Drosophila enteritis model based on MAPK pathway.

Inflammatory bowel disease (IBD) is a chronic recurrent gastrointestinal disease that seriously endangers human and animal health. Although the etiology of IBD is complex and the pathogenesis is not well understood, studies have found that genetic predisposition, diet and intestinal flora disorders are the main risk factors for IBD. The potential biological mechanism of total ginsenosides (TGGR) in the treatment of IBD remains to be elucidated. Surgery is still the main strategy for the treatment of IBD, due to the relatively high side effects of related drugs and the easy development of drug resistance. The purpose of the present study was to evaluate the efficacy of TGGR and explore the effect of TGGR on the intestinal inflammation induced by sodium dodecyl sulfate (SDS) in Drosophila and to initially explain the improvement effect and mechanism of TGGR on Drosophila enteritis by analyzing the levels of Drosophila-related proteins. During the experiment, the survival rate, climb index and abdominal characteristics of the Drosophila was recorded. Intestinal samples of Drosophila were collected for analysis of intestinal melanoma. The oxidative stress related indexes of catalase, superoxide dismutase and malondialdehyde were determined by spectrophotometry. Western blotting detected the expression of signal pathway-related factors. The effects of TGGR on growth indices, tissue indices, biochemical indices, signal pathway transduction and related mechanisms of SDS-induced Drosophila enteritis model were studied. The results showed that TGGR could repair SDS-induced enteritis of Drosophila through MAPK signaling pathway, improve survival rate and climbing ability and repair intestinal damage and oxidative stress damage. The results suggested that TGGR has potential application value in the treatment of IBD and its mechanism is related to the downregulation of phosphorylated (p)-JNK/p-ERK levels, which provides a basis for drug research in the treatment of IBD.

A dose-dependent increase in the risk of inflammatory bowel disease after exposure to broad-spectrum antibiotics: A national population study in Korea.

The association between antibiotic use and risk of inflammatory bowel disease (IBD), particularly among adults, remains unclear. Furthermore, there is a scarcity of data among non-Western countries. To investigate the association and dose-response relationships between antibiotic use and subsequent IBD risk across all ages METHODS: This population-based case-control analysis used data from the Korean National Health Insurance Service database (2004-2018). We compared 68,633 patients with new-onset IBD to matched controls (n = 343,165) using multivariable conditional logistic regression analysis. We also examined the dose-response relationship using non-linear regression analysis, and separately analysed childhood-onset IBD (aged ≤14 years) risk following early-life antibiotic exposure. The mean age at diagnosis was 45.2 ± 16.8 years. Antibiotic prescriptions between 2 and 5 years before diagnosis significantly increased the odds of developing IBD (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI]: 1.21-1.27). Additionally, sensitivity analysis revealed an elevated risk up to 9 years before diagnosis. Broad-spectrum antibiotics increased IBD risk, independent of gastroenteritis. A distinct dose-response relationship was observed irrespective of the IBD subtype and study population (all p < 0.001). Furthermore, antibiotic exposure within the first year of life was linked with the risk of childhood-onset IBD (OR, 1.51; 95% CI: 1.25-1.82). Broad-spectrum antibiotics dose-dependently increased the risk for IBD in the Korean population. Our findings provide a fundamental epidemiological basis for identifying antibiotic use as a significant risk factor for IBD across different environmental backgrounds.

The Interconnection Between Periodontitis and Inflammatory Bowel Disease

Abstract Objective Periodontitis, an oral infection affecting ~50% of Americans, is associated with the pathogenesis of inflammatory bowel disease (IBD), however, the contributory mechanisms remain ill defined. Previous GWAS studies have identified SNPs in the Interferon Regulatory Factor 8 (IRF8) gene as risk factors for IBD. The objective of this study was to explore the relationship between periodontitis and IBD using Irf8 knockout (KO) mice. Methods Periodontitis was induced in wild-type (WT) and Irf8 KO mice using the well-established oral ligature-induced periodontitis (LIP) model. The effects of LIP on oral bacterial colonization in the mouth and gut were measured by 16S rRNA and shotgun metagenomics sequencing. The influence of LIP on oral bacteria-mediated immune cell infiltration in the colonic mucosa was measured by flow cytometry, RT-qPCR, and ELISA. Results LIP promoted expansion of native oral pathogens and accumulation of the same species in the mouth and gut of Irf8 KO mice, which was associated with colitis development in Irf8 KO mice when compared to WT mice. LIP Irf8 KO mice exhibited ~2-fold increased infiltration of Th17 cells and ~2–4-fold decrease infiltration of Th1 and Treg cells in the colonic mucosa, which led to over production of IL17 and decreased production of IFN-γ and IL10. Similarly, IL-1β-producing cells were found to be higher in the colonic mucosa of LIP Irf8 KO vs WT mice. Resolution of periodontitis correlated with reduced intestinal load of oral bacteria and reversal of colitis in Irf8 KO mice. Conclusion Our study provides new perspectives on the pathophysiology of IBD. Irf8 deficiency along with dysbiotic oral and gut microbiota promote colitis in mice by activating IL17 and IL-1β signaling pathways.

Nutritional Status and Its Detection in Patients with Inflammatory Bowel Diseases.

Malnutrition is an important issue in patients with inflammatory bowel diseases (IBDs) including Crohn's disease (CD) and ulcerative colitis (UC). It is caused by altered digestion and absorption within the small bowel, inadequate food intake, and drug-nutrient interactions in patients. Malnutrition is an essential problem because it is related to an increased risk of infections and poor prognosis in patients. It is known that malnutrition is also related to an increased risk of postsurgery complications in IBD patients. Basic nutritional screening involves anthropometric parameters with body mass index (BMI) and others (fat mass, waist-to-hip ratio, muscle strength), medical history concerning weight loss, and biochemical parameters (including the Prognostic Nutritional Index). Besides standard nutritional screening tools, including the Subjective Global Assessment (SGA), Nutritional Risk Score 2002 (NRS 2002), and Malnutrition Universal Screening Tool (MUST), specific nutritional screening tools are used in IBD patients, such as the Saskatchewan Inflammatory Bowel Disease-Nutrition Risk Tool (SaskIBD-NR Tool and IBD-specific Nutritional Screening Tool). There is a higher risk of nutrient deficiencies (including iron, zinc, magnesium) and vitamin deficiencies (including folic acid, vitamin B12 and D) in IBD patients. Therefore, regular evaluation of nutritional status is important in IBD patients because many of them are undernourished. An association between plasma ghrelin and leptin and nutritional status in IBD patients has been observed. According to some authors, anti-tumor necrosis factor (anti-TNFα) therapy (infliximab) can improve nutritional status in IBD patients. On the other hand, improvement in nutritional status may increase the response rate to infliximab therapy in CD patients. Optimization of nutritional parameters is necessary to improve results of conservative and surgical treatment and to prevent postoperative complications in patients with IBDs. This review presents basic nutritional screening tools, anthropometric and laboratory parameters, dietary risk factors for IBDs, common nutrient deficiencies, associations between anti-TNFα therapy and nutritional status, selected features regarding the influence of nutritional status, and surgical outcome in IBD patients.

Epidemiology of Inflammatory Bowel Disease in a Cohort of US Black Women.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, are inflammatory diseases of the gastrointestinal tract. The incidence of IBD is increasing in minority populations; however, little is known about the epidemiology and disease characteristics of IBD in Black women. Our study population included participants in the Black Women's Health Study. Diagnosis of IBD was self-reported through the biennial questionnaires starting at baseline in 1995. We estimated the incidence of IBD according to age and geographic region. A follow-up supplementary questionnaire was also sent to a subset of participants who reported diagnosis of IBD to evaluate the accuracy of self-reported diagnosis and to assess disease characteristics. Through December 31, 2021, a total of 609 cases of IBD were reported, of which 142 were prevalent at baseline (prevalence, 0.24%), and 467 were incident (crude incidence rate, 33.2/100 000 person-years). The incidence of IBD was highest in the younger than 30 years age group and similar across geographic region. Among the participants who responded to the supplementary questionnaire, 57.1% had confirmed diagnosis of IBD. In a large prospective cohort of US Black women, we found that the incidence of IBD was similar to previously published estimates in US White women. Future studies should focus on identifying risk factors for IBD in Black individuals in the United States.

Long-term risk of inflammatory bowel disease after endoscopic biopsy with normal mucosa: A population-based, sibling-controlled cohort study in Sweden.

Although evidence suggests a persistently decreased risk of colorectal cancer for up to 10 years among individuals with a negative endoscopic biopsy result (i.e., normal mucosa), concerns have been raised about other long-term health outcomes among these individuals. In this study, we aimed to explore the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa. In the present nationwide cohort study, we identified all individuals in Sweden with a lower or upper gastrointestinal (GI) biopsy of normal mucosa during 1965 to 2016 (exposed, n = 200,495 and 257,192 for lower and upper GI biopsy, respectively), their individually matched population references (n = 989,484 and 1,268,897), and unexposed full siblings (n = 221,179 and 274,529). Flexible parametric model estimated hazard ratio (HR) as an estimate of the association between a GI biopsy of normal mucosa and IBD as well as cumulative incidence of IBD, with 95% confidence interval (CI). The first 6 months after GI biopsy were excluded to avoid detection bias, surveillance bias, or reverse causation. During a median follow-up time of approximately 10 years, 4,853 individuals with a lower GI biopsy of normal mucosa developed IBD (2.4%) compared to 0.4% of the population references. This corresponded to an incidence rate (IR) of 20.39 and 3.39 per 10,000 person-years in the respective groups or 1 extra estimated IBD case among 37 exposed individuals during the 30 years after normal GI biopsy. The exposed individuals had a persistently higher risk of overall IBD (average HR = 5.56; 95% CI: 5.28 to 5.85), ulcerative colitis (UC, average HR = 5.20; 95% CI: 4.85 to 5.59) and Crohn's disease (CD, average HR = 6.99; 95% CI: 6.38 to 7.66) than their matched population references. In the sibling comparison, average HRs were 3.27 (3.05 to 3.51) for overall IBD, 3.27 (2.96 to 3.61) for UC, and 3.77 (3.34 to 4.26) for CD. For individuals with an upper GI biopsy of normal mucosa, the average HR of CD was 2.93 (2.68 to 3.21) and 2.39 (2.10 to 2.73), compared with population references and unexposed full siblings, respectively. The increased risk of IBD persisted at least 30 years after cohort entry. Study limitations include lack of data on indications for biopsy and potential residual confounding from unmeasured risk or protective factors for IBD. Endoscopic biopsy with normal mucosa was associated with an elevated IBD incidence for at least 30 years. This may suggest a substantial symptomatic period of IBD and incomplete diagnostic examinations in patients with early IBD.

P862 Dietary risk factors associated with onset of IBD: a systematic literature review and meta-analysis

Abstract Background Several potential risk factors for Inflammatory Bowel Disease (IBD) have been highlighted, including dietary factors. Previous evidence has highlighted associations between high fibre, fruit, and vegetable intake and decreased risk of IBD. Conversely, low intake of dietary fibre, and low vitamin D levels are associated with incident IBD. One systematic review reported that high intake of total fats, PUFAs, and omega-6 fatty acids, were associated with an increased risk of Crohn’s Disease (CD) and Ulcerative Colitis (UC), whereas high fibre and fruit intakes were associated with decreased CD risk, and high vegetable intake was associated with decreased UC risk. Despite this evidence, there remains a paucity of literature reporting on the various dietary risk factors for IBD systematically and quantitatively. Thus, the purpose of this systematic review is to determine whether dietary factors are associated with risk of developing IBD Methods We conducted searches in the following electronic databases: Ovid MEDLINE, Web of Science, and the Cochrane Library. Keywords and search terms related to ‘diet’ and ‘inflammatory bowel disease’ were applied. This review includes case-control, cohort studies, and RCTs investigating the association between dietary factors and onset of IBD. Study protocol details have been published on the International prospective register of systematic reviews (PROSPERO). Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022290798Databases Results Our search identified 14,809 relevant articles to include, outlined in Figure 1. After title and abstract screening there were 119 articles that met the eligibility criteria. Overall, 24 articles were deemed suitable for study synthesis. When compared with those consuming the highest intake of carbohydrates, those consuming the lowest levels of carbohydrates had an overall reduced risk of IBD of 30% (RR 0.70, 95% CI 0.51-0.89) and a reduced risk of CD of 37% (RR 0.63, 95% CI 0.32-0.94). When compared with those consuming the lowest intake of vegetables, those consuming the highest levels of vegetables had an overall reduced risk of IBD of 42% (RR 0.58, 95% CI 0.53-0.63). When stratified by sub-group, those consuming the highest intake of vegetables compared with the lowest had a reduced risk of 87% of IBD (RR 0.13, 95% CI 0.04-0.22), 52% of UC (RR 0.48, 95% CI 0.24-0.71) and a reduced risk of CD of 18% (RR 0.82, 95% CI 0.76-0.88). Conclusion This systematic review provides a detailed summary of dietary factors associated with the onset of IBD. This evidence will inform on potential preventative strategies for IBD and will inform the academic community, patients, and policy makers about the role of dietary factors in the development of IBD.

INFLAMMATORY BOWEL DISEASE AND ASSOCIATED CARDIOVASCULAR DISEASE OUTCOMES: A SYSTEMATIC REVIEW

Abstract BACKGROUND There is limited and conflicting data available regarding the Cardiovascular disease outcomes associated with Inflammatory Bowel Disease (IBD) OBJECTIVE We aim to perform a systematic review to evaluate the cardiovascular outcomes and mortality associated with IBD patients. METHODS A systematic literature search has been performed on PubMed, Embase, Cochrane, and Scopus from inception till May 2022 without any language restrictions. RESULTS A total of 2,029,941 patients were included into the analysis from 16 studies. The mean age of the patients was 45.6 years. More females were found compared with males (57% vs 43%). The most common risk factors for Cardiovascular disease (CVD) included smoking (24.19%) and alcohol (4.60%). The most common co-morbidities included hypertension (30%), diabetes mellitus (14.41%), dyslipidemia (18.42%), previous CVD (22%), and renal disease (10%). Among outcomes All-cause mortality among IBD patients was 1.66%; Ulcerative Colitis (UC): 15.92%; and Crohn’s disease (CD): 0.30%. Myocardial Infarction (MI) among IBD patients were 1.47%, among UC: 30.96%; and among CD: 34.14%. Cardiovascular Death (CVD) events among IBD patients were 1.95%. Heart failure events among IBD patients were 5.49%, while Stroke events among IBD Patients were 0.95%; among UC: 2.63%; and CD: 2.41% respectively. CONCLUSION There was a possible association between IBD patients and adverse cardiovascular outcomes especially in young and females. Though there remains a lack of concrete treatment algorithms and assessment parameters that better characterize IBD risk factors, nutritional modifications and physical activity should be at the fore-front of CVD prevention in IBD.

Prevalence and Risk Factors Associated With Inflammatory Bowel Disease in Patients Using Proton-Pump Inhibitors: A Population-Based Study.

Background and aim Proton pump inhibitor (PPI) is a heavily prescribed medication in the United States that is used to treat several gastrointestinal disorders. Although it has been considered to besafe compared to other medications, multiple gastrointestinal side effects have been reported. These effects of PPIs might stemfrom the progressive alteration of the intestinal microbiome. Patients with inflammatory bowel disease (IBD) using PPI are also seen to be less likely to achieve remission. However, in the current literature, there is very little evidence of the risk of developing IBD in patients who have been using PPIs. Therefore, our aim was to perform a cross-sectional population-based study with in-depth analysis to assess the prevalence and risk factors of IBD amongst PPI users in the United States. Methodology A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. A cohort of patients with a diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) between 1999-2022 was identified using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). Patients aged 18 to 65 years were included. We excluded any individual who had a diagnosis of chronic liver disease, autoimmune disease (excluding IBD), or cancer. The risk of IBD was calculated using a multivariate regression analysis to account for potential confounders includingnon-steroidal anti-inflammatory drugs (NSAIDs) use, smoking, patients who have had a diagnosis of alcoholism, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and metabolic syndrome. A two-sided P-value <0.05 was considered statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). Results A total of 79,984,328 individuals were screened in the database and 45,586,150 patients were selected in the final analysis after accounting for inclusion and exclusion criteria.Using multivariate regression analysis, the risk of developing UC and CD was calculated. The odds of having UC amongst patientson PPI was 2.02 (95%CI 1.98-2.06), P-value <0.001.Similarly, the odds of having CD were high amongst PPI users (OR 2.79, 95%CI 2.75-2.84), P- value <0.001 Conclusion Our study demonstrates that patients on PPIs are frequently found to have UC and CD even when adjusting for common risk factors.Hence, we urge clinicians to be aware of this association in order to limit unnecessary prescriptions of PPIs, especially for patients who are at risk for autoimmune diseases.

Obesity among those newly diagnosed with Crohn’s disease and ulcerative colitis compared with the general population

ObjectiveObesity is a potentially modifiable risk factor for inflammatory bowel disease (IBD). We aimed to evaluate the body mass index (BMI) of those diagnosed with IBD early versus late in...

Pioglitazone Has a Null Association with Inflammatory Bowel Disease in Patients with Type 2 Diabetes Mellitus.

Pioglitazone shows potential benefits in inflammatory bowel disease (IBD) in preclinical studies, but its effect in humans has not been researched. We used a nationwide database of Taiwan's National Health Insurance to investigate whether pioglitazone might affect IBD risk. We enrolled 12,763 ever users and 12,763 never users matched on a propensity score from patients who had a new diagnosis of type 2 diabetes mellitus between 1999 and 2008. The patients were alive on 1 January 2009, and they were followed up for a new diagnosis of IBD until 31 December 2011. Propensity score-weighted hazard ratios were estimated, and the interactions between pioglitazone and major risk factors of IBD (i.e., psoriasis, arthropathies, dorsopathies, chronic obstructive pulmonary disease/tobacco abuse, and any of the above) and metformin were investigated. At the end of the follow-up, 113 ever users and 139 never users were diagnosed with IBD. When compared to never users, the hazard ratio for ever users was 0.809 (95% confidence interval: 0.631-1.037); and none of the hazard ratios for ever users categorized by tertiles of cumulative duration and cumulative dose reached statistical significance. No interactions with major risk factors or metformin were observed. Our findings suggested a null effect of pioglitazone on IBD.

Occurrence of inflammatory bowel disease in patients with chronic inflammatory skin diseases: a cohort study: Classification: Epidemiology.

Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) in a range of data sources with mixed conclusions. We compared the incidence of IBD - ulcerative colitis (UC) and Crohn disease (CD) - in patients with a CISD vs. similar persons without a CISD. In this cohort study using nationwide, longitudinal, commercial insurance claims data from the USA, we identified adults and children who were seen by a dermatologist between 2004 and 2020, and diagnosed with either psoriasis, atopic dermatitis, alopecia areata, vitiligo or hidradenitis suppurativa. Comparator patients were identified through risk-set sampling; they were eligible if they were seen by a dermatologist at least twice and not diagnosed with a CISD. Patient follow-up lasted until either IBD diagnosis, death, disenrolment or end of data stream, whichever came first. IBD events, UC or CD, were identified via validated algorithms: hospitalization or diagnosis with endoscopic confirmation. Incidence rates were computed before and after adjustment via propensity-score decile stratification to account for IBD risk factors. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated to compare the incidence of IBD in CISD vs. non-CISD. We identified patients with atopic dermatitis (n = 123 614), psoriasis (n = 83 049), alopecia areata (n = 18 135), vitiligo (n = 9003) or hidradenitis suppurativa (n = 6806), and comparator patients without a CISD (n = 2 376 120). During a median follow-up time of 718 days, and after applying propensity-score adjustment for IBD risk factors, we observed increased risk of both UC (HRUC 2·30, 95% CI 1·61-3·28) and CD (HRCD 2·70, 1·69-4·32) in patients with hidradenitis suppurativa, an increased risk of CD (HRCD 1·23, 1·03-1·46) but not UC (HRUC 1·01, 0·89-1·14) in psoriasis, and no increased risk of IBD in atopic dermatitis (HRUC 1·02, 0·92-1·12; HRCD 1·08, 0·94-1·23), alopecia areata (HRUC 1·18, 0·89-1·56; HRCD 1·26, 0·86-1·86) or vitiligo (HRUC 1·14, 0·77-1·68; HRCD 1·45, 0·87-2·41). IBD was increased in patients with hidradenitis suppurativa. CD alone was increased in patients with psoriasis. Neither UC nor CD was increased in patients with atopic dermatitis, alopecia areata or vitiligo. What is already known about this topic? Several studies have linked various chronic inflammatory skin diseases (CISDs) with inflammatory bowel disease (IBD) utilizing a range of data sources, with mixed conclusions. What does this study add? This large-scale, claims-based cohort study expands current knowledge by providing background rates for IBD across multiple CISDs using consistent methods and within a single, nationally representative patient population. We observed a relative increased risk of IBD in patients with hidradenitis suppurativa, but the overall incidence rate difference of IBD was generally low. Crohn disease alone was significantly increased in patients with psoriasis, and neither ulcerative colitis nor Crohn disease was increased in patients with atopic dermatitis, vitiligo or alopecia areata.

Involvement of HHV-4 (Epstein-Barr Virus) and HHV-5 (Cytomegalovirus) in Inflammatory Bowel Disease and Colorectal Cancer: A Meta-Analysis.

Simple SummaryThe prevalence of colorectal cancer (CRC) and inflammatory bowel disease (IBD) is increasing worldwide. Understanding what factors foster these diseases’ development can help reduce their burden. Viral infections have been suggested to be involved in the genesis of these diseases, but the data is contradictory. The present study analyzed 11,413 articles on the topic and identified 196 that could provide information on the relationship between a viral infection and these gastrointestinal diseases. The Epstein–Barr virus (EBV, HHV-4) was strongly associated with IBD, and cytomegalovirus (HHV-5) with both CRC and IBD.Gastrointestinal diseases (GDs) include colorectal cancer (CRC), gastric cancer (GC), and inflammatory bowel disease (IBD). CRC and GC are typically diagnosed at later stages of development, reducing patients’ chances of survival. IBD is characterized by chronic intestinal inflammation and is a significant risk factor for the development of CRC. Chronic bacterial infections have been shown to promote some GDs, but the role of viruses in the etiology of these diseases is less clear. The present meta-analysis retrieved literature on the viral prevalence in GD patients, measuring the GD risk in odd ratios. By quantifying the study heterogeneity, the literature bias was fundamentally included in the analysis. The analysis also included 11 metagenomic studies. Our meta-analysis retrieved 11,413 studies, with 196 suitable for analysis. HHV-4 (Epstein–Barr virus) was identified as a significant risk factor for the development of IBD, and HHV-5 (cytomegalovirus) as a risk factor for both CRC and IBD. Polyomaviruses and the Hepatitis B virus were also, less strongly, involved in the risk of CRC and IBD. No relations withstanding the literature bias were identified for GC. The study discusses these findings, as well as the role of other viruses in the etiology of CRC and IBD.