BACKGROUND:Organoid is an in vitro three-dimensional organ-bud that shows realistic microanatomy and physiological relevance.The progress in generating organoids that faithfully recapitulate human in vivo tissue composition has extended organoid applications from being just a basic research tool to a translational platform with a wide range of uses.Study of hostmicrobial interactions relies on model systems to mimic the in vivo infection.Researchers have developed various experimental models in vitro and in vivo to examine the dynamic host-microbial interactions.For some infectious pathogens,model systems are lacking whereas some of the used systems are far from optimal.OBJECTIVE:In the present work,we will review the brief history and recent findings using organoids for studying hostmicrobial interactions.METHODS:A systematic literature search was performed using the PubMed search engine.We also shared our data and research contnbution to the field.RESULTS:we summarize the brief history of 3D organoids.We discuss the feasibility of using organoids in studying hostmicrobial interactions,focusing on the development of intestinal organoids and gastric organoids.We highlight the advantage and challenges of the new experimental models.Further,we discuss the future direction in using organoids in studying hostmicrobial interactions and its potential application in biomedical studies.CONCLUSION:In combination with genetic,transcriptome and proteomic profiling,both murine-and human-derived organoids have revealed crucial aspects of development,homeostasis and diseases.Specifically,human organoids from susceptible host will be used to test their responses to pathogens,probiotics,and drugs.Organoid system is an exciting tool for studying infectious disease,microbiome,and therapy.