Gastrointestinal Organoids: Understanding the Molecular Basis of the Host–Microbe Interface

David R Hill, Jason R Spence

Abstract

In recent years, increasing attention has been devoted to the concept that microorganisms play an integral role in human physiology and pathophysiology. Despite this, the molecular basis of host–pathogen and host–symbiont interactions in the human intestine remains poorly understood owing to the limited availability of human tissue, and the biological complexity of host–microbe interactions. Over the past decade, technological advances have enabled long-term culture of organotypic intestinal tissue derived from human subjects and from human pluripotent stem cells, and these in vitro culture systems already have shown the potential to inform our understanding significantly of host-microbe interactions. Gastrointestinal organoids represent a substantial advance in structural and functional complexity over traditional in vitro cell culture models of the human gastrointestinal epithelium while retaining much of the genetic and molecular tractability that makes in vitro experimentation so appealing. The opportunity to model epithelial barrier dynamics, cellular differentiation, and proliferation more accurately in specific intestinal segments and in tissue containing a proportional representation of the diverse epithelial subtypes found in the native gut greatly enhances the translational potential of organotypic gastrointestinal culture systems. By using these tools, researchers have uncovered novel aspects of host–pathogen and host–symbiont interactions with the intestinal epithelium. Application of these tools promises to reveal new insights into the pathogenesis of infectious disease, inflammation, cancer, and the role of microorganisms in intestinal development. This review summarizes research on the use of gastrointestinal organoids as a model of the host–microbe interface.