Gastrointestinal tract modeling using organoids engineered with cellular and microbiota niches

The recent emergence of organoid technology has attracted great attention in gastroenterology because the gastrointestinal (GI) tract can be recapitulated in vitro using organoids, enabling disease modeling and mechanistic studies. However, to more precisely emulate the GI microenvironment in vivo, several neighboring cell types and types of microbiota need to be integrated into GI organoids. This article reviews the recent progress made in elucidating the crosstalk between GI organoids and components of their microenvironment. We outline the effects of stromal cells (such as fibroblasts, neural cells, immune cells, and vascular cells) on the gastric and intestinal epithelia of organoids. Because of the important roles that microbiota play in the physiology and function of the GI tract, we also highlight interactions between organoids and commensal, symbiotic, and pathogenic microorganisms and viruses. GI organoid models that contain niche components will provide new insight into gastroenterological pathophysiology and disease mechanisms. Miniature guts and stomachs grown in the laboratory together with supporting cells and microbes provide a physiologically relevant model for studying gastrointestinal disease and testing candidate drug therapies. In a review article, Seung-Woo Cho and colleagues from Yonsei University, Seoul, South Korea, discuss the latest approaches scientists and drug developers are using to coax collections of stem cells into gut-like structures that best reproduce the biology of the human stomach and intestines. To precisely emulate the gastrointestinal environment, researchers have begun integrating cells from neighboring connective tissues, including structural cells, neural cells, and immune cells, along with resident bacteria and viruses that contribute to health and disease. Techniques such as bioprinting and microfluidics, and new biomaterials are being used to mimic the three-dimensional architecture of the digestive tract on a small scale.