Engineered Human Gastrointestinal Cultures to Study the Microbiome and Infectious Diseases

Abstract

New models to study the intestine are key to understanding intestinal diseases and developing novel treatments. Intestinal organ-like culture systems (organoids and enteroids) have substantially advanced the study of the human gastrointestinal tract. Stem cell-derived cultures produce self-organizing structures that contain the multiple differentiated intestinal epithelial cell types including enterocytes, goblet, Paneth, and enteroendocrine cells. Understanding host-microbial interactions is one area in which these cultures are expediting major advancements. This review discusses how organoid and enteroid cultures are biologically and physiologically relevant systems to investigate the effects of commensal organisms and study the pathogenesis of human infectious diseases. These cultures can be established from many donors and they retain the genetic and biologic properties of the donors, which can lead to the discovery of host-specific factors that affect susceptibility to infection and result in personalized approaches to treat individuals. The continued development of these cultures to incorporate more facets of the gastrointestinal tract, including neurons, immune cells, and the microbiome, will unravel new mechanisms regulating host-microbial interactions with the long-term goal of translating findings into novel preventive or therapeutic treatments for gastrointestinal infections.

Keywords: 3D, three-dimensional; Enteroids; HBGA, histo-blood group antigen; Host-Microbial Interactions; IFN, interferon; IL, interleukin; Infections; Microbiome; Organoids.

Figure 1

Derivation of organoids and enteroids and modes of exposure to microbial organisms in three-dimensional or two-dimensional format. Modified from Mills and Estes.

Figure 2

Future platform development of enteroids and organoids to facilitate studies with microbial organisms.