True to type: From human biopsy to complex gut physiology on a chip

The small intestine is the main site where we digest and absorb nutrients and minerals from food, and it is also a place where many intestinal infections occur and digestive and inflammatory disorders manifest themselves. To better understand the intestine in its normal and pathological states, researchers have created “organoids” by isolating intestinal stem cells from human biopsy samples. These organoids form all of the cell types present in human intestine, but they grow as cysts surrounded by thick extracellular matrix gels with their “apical” cell surface (which is normally exposed to the content of the gut) facing an enclosed lumen. This prevents the study of dynamic processes involving the intestinal barrier, including nutrient and drug transport, as well as its interactions with the microbiome. In addition, organoids lack a vasculature and the mechanical movements caused by normal peristalsis and blood flow, which are vital for many processes in the gut, including its regeneration and control of bacterial overgrowth.