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BACKGROUND & AIMS: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers. METHODS: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio (LMR); gut inflammation via fecal calprotectin (FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. RESULTS: Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5 and 15 (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.40-0.96; P = .034), and living with a large family size in the first year of life (HR, 0.43; 95% CI, 0.21-0.85; P = .016) were associated with decreased CD risk, whereas having a bird at the time of recruitment (HR, 2.78; 95% CI, 1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity, whereas bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. CONCLUSION: This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis.
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Objectives: Irritable bowel syndrome (IBS) is a chronic, debilitating, functional gastrointestinal disorder with symptoms of abdominal pain, bloating, and altered bowel behaviours of constipation (IBS-C), diarrhea (IBS-D), or a mixture of both (IBS-M). There is limited information published on the impact of symptoms on everyday life in the Canadian population. Methods: An online survey was conducted with individuals diagnosed with IBS to capture the severity and frequency of patient-reported symptoms, including impact on productivity, quality of life, healthcare utilization, treatment access, and corresponding symptom relief. Responses from the three subtypes of IBS were categorized to illustrate differences among these. Results: There were 2,470 qualified respondents (filtered from 2,981, which included nonspecific IBS). IBS-M was the most common subtype, at 44 percent. Most individuals from all three IBS subtypes reported experiencing moderate to severe abdominal pain (63-70 percent) and bloating (59-75 percent) over the previous 3 months. Persons living with IBS-C reported severe bloating (32 percent), straining (72 percent), and tenesmus (78 percent) whereas those with IBS-D experienced severe urgency (63 percent) and incontinence (29 percent). Symptoms interfered in daily life, sometimes in 46 percent and often in 23 percent of respondents. Patients reported mood and anxiety disorders as common comorbidities with IBS (mood disorders: 30-34 percent; anxiety disorders: 25-30 percent). Conclusions: This study focuses on the differences among the IBS subtypes. IBS impacts productivity and healthcare utilization, which requires further investigation on approaches to improve treatment. The frequency and severity of symptoms in IBS are high and only a few respondents reported that their symptoms are under control.