Gene expression profiles in human duodenal organoid-derived monolayer

The human small intestine is the key organ for absorption, metabolism, and excretion of orally administered drugs. To preclinically predict these reactions in drug discovery research, a cell model that can precisely recapitulate the in vivo human intestinal monolayer is desired. Here, we developed a monolayer platform using human biopsy-derived duodenal organoids for application to pharmacokinetic studies. The human duodenal organoid-derived monolayer was prepared by a simple method in 3–8 days. It consisted of polarized absorptive cells and had a barrier function. It showed much higher cytochrome P450 (CYP) 3A4 and carboxylesterase (CES) 2 activities than Caco-2 cells. It also showed efflux activity of P-glycoprotein (P-gp) and inducibility of CYP3A4. Finally, its gene expression profile was closer to the adult human duodenum, compared to the profile of Caco-2 cells. Based on these findings, this monolayer assay system using biopsy-derived human intestinal organoids is likely to be widely adopted. Human adult duodenal biopsies, human duodenal organoids, human duodenal organoid-derived monolayer, and Caco-2 cells were subjected to DNA microarray analysis. Human adult duodenal biopsies were pooled from 5-donor samples (excluding the material used to make the organoids). Human duodenal organoids, the human duodenal organoid-derived monolayer, and Caco-2 cells were pooled from triplicate samples of one independent experiments.