Bernstein CN, Shanahan F. Disorders of a modern lifestyle: reconciling the epidemiology of inflammatory bowel diseases

University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, Winnipeg, Manitoba, Canada.
Gut (Impact Factor: 14.66). 06/2008; 57(9):1185-91. DOI: 10.1136/gut.2007.122143
Source: PubMed


A lasting lesson for gastroenterologists was the failure of traditional epidemiologic approaches to raise the possibility of a transmissible agent as a cause of peptic ulcer disease. Another lesson was that the solution to some human disorders can never be found by reliance on research focused exclusively on the human host, without due reference to the interface with the microbial environment. In the case of inflammatory bowel diseases (IBD), excessive reliance on conventional risk factor epidemiology without adequate rapprochement with concepts of disease mechanisms is likely to provide more controversy, conflict and confusion than consensus. However, the changing epidemiology of IBD associated with societal transition from developing to developed status is of such consistency that it represents a model, and may facilitate reconciling disparate lifestyle and environmental factors with causal mechanisms.

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    • "With more than 1.4 million people affected in the United States (CCFA, 2015), IBD poses an urgent challenge to understand the link between microbiota and human health. The development of IBD depends on a diverse set of factors including lifestyle (Bernstein and Shanahan, 2008), environment (Danese et al., 2004), and genetic predisposition (Jostins et al., 2012). Gut microbes also contribute to IBD, and deviations from the microbial composition of the healthy human gut have been detected in patients with long-standing or newly diagnosed IBD (Gevers et al., 2014;Papa et al., 2012). "
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    ABSTRACT: The relationship between the host and its microbiota is challenging to understand because both microbial communities and their environments are highly variable. We have developed a set of techniques based on population dynamics and information theory to address this challenge. These methods identify additional bacterial taxa associated with pediatric Crohn disease and can detect significant changes in microbial communities with fewer samples than previous statistical approaches required. We have also substantially improved the accuracy of the diagnosis based on the microbiota from stool samples, and we found that the ecological niche of a microbe predicts its role in Crohn disease. Bacteria typically residing in the lumen of healthy individuals decrease in disease, whereas bacteria typically residing on the mucosa of healthy individuals increase in disease. Our results also show that the associations with Crohn disease are evolutionarily conserved and provide a mutual information-based method to depict dysbiosis.
    Full-text · Article · Jan 2016 · Cell Reports
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    • "UC mainly affects the mucosa of the colon and rectum, whereas inflammation in CD may occur in any part of the gastrointestinal tract [2]. The incidence of IBD, particularly CD, has dramatically increased in industrialized nations over the last decades, however, the exact etiology of IBD still remains unclear [3]. Several factors were reported to play a role in IBD pathogenesis such as environmental factors, diet, genetic factors and the immune system [1]. "
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    ABSTRACT: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. Though its exact etiology is still unclear, it is proposed that an imbalance in the intestinal homeostasis leads to a disturbed interaction between commensal microbiota and the mucosal immune system. Previous studies have shown that both innate and adaptive immunity are involved in an overwhelming colon inflammation, and thus contribute to the pathogenesis of IBD. In innate immunity, several pattern recognition receptors such as Toll-like receptors, NOD-like receptors or C-type lectin receptors (CLRs) are involved in IBD pathogenesis. Myeloid CLRs are mainly expressed by antigen-presenting cells and bind to glycan structures present on self or foreign antigens. The Macrophage-restricted C-type lectin (MCL) and the Dendritic cell immunoreceptor (DCIR) are two poorly characterized members of the CLR family. In this study, we investigated the role of MCL and DCIR in the pathogenesis of murine colitis. Both CLRs bound to intestinal microbiota to a different extent. They modulated the production of pro-inflammatory cytokines by antigen-presenting cells upon stimulation with heat-killed microbiota and impacted subsequent T cell responses. To analyze whether MCL and DCIR contribute to the pathogenesis of IBD, the dextran sulfate sodium (DSS) murine colitis model was employed. MCL-/- as well as DCIR-/- mice exhibited only a slightly increased severity of disease compared to wild-type mice indicating a limited role for MCL and DCIR in the regulation of intestinal immunity.
    Full-text · Article · Jul 2014 · PLoS ONE
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    • "An immigration study from British Columbia suggests that compared to the natives, South Asian pediatric 2nd generation immigrants not only adapt the incidence rate in the new country, they actually show higher incidence rates of IBD [28]. In another study, this was not the case for the adult immigrants, suggesting that age at the time of migration is crucial [29]. "
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    ABSTRACT: Background The two inflammatory bowel diseases (IBD), ulcerative colitis and Crohn's disease, has increased rapidly during the twentieth century, but the aetiology is still poorly understood. Impaired immunological competence due to decreasing biodiversity and altered microbial stimulation is a suggested explanation. Objective Place of upbringing was used as a proxy for the level and diversity of microbial stimulation to investigate the effects on the prevalence of IBD in adulthood. Methods Respiratory Health in Northern Europe (RHINE) III is a postal follow-up questionnaire of the European Community Respiratory Health Survey (ECRHS) cohorts established in 1989-1992. The study population was 10,864 subjects born 1945-1971 in Denmark, Norway, Sweden, Iceland and Estonia, who responded to questionnaires in 2000-2002 and 2010-2012. Data were analysed in logistic and Cox regression models taking age, sex, smoking and body mass index into consideration. Results Being born and raised on a livestock farm the first 5 years of life was associated with a lower risk of IBD compared to city living in logistic (OR 0.54, 95 % CI 0.31; 0.94) and Cox regression models (HR 0.55, 95 % CI 0.31; 0.98). Random-effect meta-analysis did not identify geographical difference in this association. Furthermore, there was a significant trend comparing livestock farm living, village and city living (p < 0.01). Sub-analyses showed that the protective effect was only present among subjects born after 1952 (OR 0.25, 95 % CI 0.11; 0.61). Conclusion This study suggests a protective effect from livestock farm living in early childhood on the occurrence of IBD in adulthood, however only among subjects born after 1952. We speculate that lower microbial diversity is an explanation for the findings.
    Full-text · Article · Jun 2014 · European Journal of Epidemiology
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