An impaired interaction between the gut and the intestinal microbiome is likely to be the key element in the pathogenesis of Crohn's disease (CD). Family studies have provided invaluable information on CD pathogenesis and on its etiology. Relatives share the same genetic risk of developing the disease as affected subjects. Relatives also exhibit similar features relating to their host-microbiome interaction, namely genetic variants in loci involved in detecting bacteria, a greater sero-reactivity to microbial components, and an impaired intestinal permeability. The burden of environmental factors such as cigarette smoking and dysbiosis also seems to be particularly relevant in these genetically predisposed subjects. Diet is emerging as an important factor and could account for the changing epidemiology of CD in recent years. Despite the pivotal role of genetics in the disease's pathogenesis (especially in familial CD), screening tests in healthy relatives cannot be recommended.
Keywords: Crohn’s disease; Environment; Genetics; Microbiome; Relatives.