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.

Gut microbiome in hematopoietic stem cell transplantation: patient- and treatment-related factors

“…Relations of NOD/CARD system and other gut disorders is also confi rmed by the results of Hrnčířová et al [71] concerning distinct associations between Crohn's disease and some gene variants of CARD15/NOD2 gene.…”

Gastrointestinal dysbiosis and Escherichia coli pathobionts in inflammatory bowel diseases

“…Importantly, the early finding of a defect in the caspase recruitment domain family, member 15 ( NOD2/CARD15 ) gene among CD patients, has reawakened the search for specific involved pathogens [28]. NOD2/CARD15 is involved in the innate immune system including the production of defensins; therefore, defects in this gene could imply that the host is more susceptible to gastrointestinal infections [29]. It has, furthermore, been shown that the number of viable internalized Salmonella typhimurium in Caco‐2 cells was higher when the Caco‐2 cells were transfected with a variant CARD15/NOD2 expression plasmid associated with Crohn's disease [30].…”