Brown, Monica E.; Gleizes, Antoine R.; Yu, Qianhui; Adhikari, Upasana Das; Nagarajan, Rekha; Rout, Prateeksha; Camp, J. Gray; Yilmaz, Omer H.; Tape, Christopher J.; Tyska, Matthew J.; Verzi, Michael P.; Lau, Ken S.; Gracz, Adam D. (2026).听.听Cellular and Molecular Gastroenterology and Hepatology, 20(10), 101832.听
Organoids are miniature, laboratory-grown versions of organs that can mimic important features of the human intestine. Since intestinal organoids were first developed from human tissue in 2011, advances in laboratory methods have made them increasingly useful for studying gastrointestinal biology and disease. However, it remains important to determine how accurately and consistently these models represent the real human intestine. This commentary reviews current methods for comparing small intestinal and colon organoids with native tissues, discusses their strengths and limitations, and proposes approaches for improving their accuracy and reproducibility. These efforts will help establish organoids as reliable models for studying human gastrointestinal health and disease.
Figure 1聽
Benchmarking human GI organoids across scales.听Comparing native GI tissue with organoid models requires multiple approaches that capture different aspects of small intestinal and colonic function. The crypt鈥搗illus axis of the small intestine, with a lack of villi in the colon not represented here, as compared with organoids, shows differences in architecture or cell types that can be ascertained using classical imaging techniques. Beyond morphology, assessments of DNA accessibility, epigenomics, gene expression, proteomics, and metabolomics probe distinct aspects of GI and organoid functionality (A). Many of these biological scales have methods that can be performed at either bulk or single-cell resolution: bulk analyses capture overall tissue or organoids characteristics, whereas single-cell approaches reveal cell-specific changes that can be masked by bulk measurements (B).