Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science
Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science
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assignment_turned_in ProjectFrom 2018Partners:Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science, MICROBES, INTESTIN, INFLAMMATION ET SUSCEPTIBILITÉ DE LHÔTE, University of Clermont AuvergneDepartment of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Science,MICROBES, INTESTIN, INFLAMMATION ET SUSCEPTIBILITÉ DE LHÔTE,University of Clermont AuvergneFunder: French National Research Agency (ANR) Project Code: ANR-17-CE17-0017Funder Contribution: 243,000 EURInflammatory bowel diseases (IBD), including Crohn's disease (CD), are contemporary conditions of industrialized societies. The global evolution of IBD implicates a potential sequence in the pathogenesis of IBD: Westernization alters environmental exposure that influences the microbiome that incites IBD in genetically susceptible individuals. Understanding the elements of this sequence is critical in order to halt the progression of IBD. The lifetime risk of developing IBD has been calculated to be 1%. All ages can be affected but CD mostly begins in young adulthood. It has been estimated that over 2 million people are affected with IBD in Europe. In newly industrialized countries, the incidence of IBD especially that of CD has been increasing. Consequently, slowing down the incidence of CD is paramount. Experimental and observational data suggest that intestinal inflammation in CD arises from abnormal immune response to intestinal microbiota in genetically susceptible individuals. Genes that regulate innate immune response, intestinal barrier function and bacteria killing of intracellular pathogens have been associated with an increased risk for developing CD in Caucasian populations. The search for specific pathogens in CD has identified in the intestinal mucosa of patients several candidates. One with much supporting evidence is the adherent invasive Escherichia coli (AIEC). Since its discovery, several groups have reported a higher prevalence of AIEC in CD patients compared to healthy subjects and confirmed their pro-inflammatory potential. A growing body of work indicates that different host environments can select such AIEC pathobiont. AIEC colonization in mice leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD. Furthermore the presence of AIEC in mucosa of CD patients at diagnosis suggests they may play a role in early stages of disease onset. Much of the work on this organism, and its potential role in CD, has been undertaken in areas of high CD incidence (Europe, North America and Australia). It is currently unclear if the changes in such putative pathogens organisms identified in Western populations are more widespread in IBD patients in regions with increasing IBD incidence, especially in Asia. Information is also lacking about the degree of genetic variation between the bacteria assigned to these taxonomic groups from different ethnic and geographical regions. The significance of AIEC pathobiont in the pathogenesis of CD worldwide is currently unknown. For this organism to be considered truly implicated in CD, its presence in patients in other parts of the world including countries with high disease incidence and countries with increasing incidence would need to be demonstrated. In the past few decades, the incidence of CD is increasing in developing countries. In 2011, the first and largest population-based study was conducted by our group consisting of 13 countries in Asia-Pacific. We showed that Hong Kong is amongst the top three countries in Asia with the highest incidence of CD. The incidence of CD in Hong Kong has increased by 30-fold in the past two decades. In addition, CD incidence varies between rural and urban area within China, with a higher incidence in urban areas, likely as the result of the influence of environmental factors including diet. The main objective of this study is to assess the prevalence, characteristics and genetics of pathogenic AIEC in ileal CD across two different distinct populations and geography (Caucasians in France and Chinese in Hong-Kong) and to delineate therapeutics targeting AIEC in individuals with Crohn’s disease. These data will provide an improved understanding on whether AIEC is a risk factor for Crohn’s disease globally, the pathogenicity of AIEC and possible treatment based on AIEC eradication in Crohn’s disease which can lead to a personalized therapeutic case based approach in patients with Crohn’s disease.
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