title: Crohn's disease: a role of gut microbiota and Nod2 gene polymorphisms in disease pathogenesis.
abstract: Crohn's disease is a chronic immune-mediated intestinal inflammation targeted against a yet incompletely defined subset of commensal gut microbiota and occurs on the background of a genetic predisposition under the influence of environmental factors. Genome-wide association studies have identified about 70 genetic risk loci associated with Crohn's disease. The greatest risk for Crohn's disease represent polymorphisms affecting the CARD15 gene encoding nucleotide-binding oligomerization domain 2 (NOD2) which is an intracellular sensor for muramyl dipeptide, a peptidoglycan constituent of bacterial cell wall. The accumulated evidence suggests that gut microbiota represent an essential, perhaps a central factor in the induction and maintaining of Crohn's disease where dysregulation of normal co-evolved homeostatic relationships between intestinal microbiota and host mucosal immune system leads to intestinal inflammation. Taken together, these findings identify Crohn's disease as a syndrome of overlapping phenotypes that involves variable influences of genetic and environmental factors. A deeper understanding of different genetic abnormalities underlying Crohn's disease together with the identification of beneficial and harmful components of gut microbiota and their interactions are essential conditions for the categorization of Crohn's disease patients, which enable us to design more effective, preferably causative, individually tailored therapy.
authors: Department of Clinical Immunology and Allergology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Králové, Czech Republic.
authors: Lucia
authors: L
authors: Hrnčířová
authors: Department of Clinical Immunology and Allergology, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Králové, Czech Republic.
authors: Jan
authors: J
authors: Krejsek
authors: Department of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Doly 183, 549 22 Nový Hrádek, Czech Republic.
authors: Igor
authors: I
authors: Šplíchal
authors: Department of Immunology and Gnotobiology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Doly 183, 549 22 Nový Hrádek, Czech Republic.
authors: Tomáš
authors: T
authors: Hrnčíř
mesh_terms: D003424:Crohn Disease / Q000235:genetics*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D064307:Microbiota; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D053473:Nod2 Signaling Adaptor Protein