CRISPR/Cas9 genome editing technology has been employed to develop genetically defined cultures from organoids.151–154 The manipulation of specific genes linked to genetic susceptibility could help gain a better understanding of disease mechanisms, also in relation to microbial exposure [eg, GATM, NOD2, HNF4A, ATG16L1,... ]].155 Such models could be employed to dissect the role of epithelium in early-onset IBD, where a specific genetic mutation of the intestinal epithelium causes a defect in barrier function156 and no inflammation has developed yet. The gene discussed is HNF4A; the disease is inflammatory bowel disease.