Intestinal Organoids: A Tool for Modelling Diet–Microbiome–Host Interactions

Dietary patterns, microbiome dysbiosis, and gut microbial metabolites (GMMs) have a pivotal role in the homeostasis of intestinal epithelial cells and in disease progression, such as that of colorectal cancer (CRC). Although GMMs and microorganisms have crucial roles in many biological activities, models for deciphering diet–microbiome–host relationships are largely limited to animal models. Thus, intestinal organoids (IOs) have provided unprecedented opportunities for the generation of in vitro platforms with the sufficient level of complexity to model physiological and pathological diet–microbiome–host conditions. Overall, IO responses to GMM metabolites and microorganisms can provide new insights into the mechanisms by which those agents may prevent or trigger diseases, significantly extending our knowledge of diet–microbiome–host interactions. Dietary patterns modulate the gut microbiota and alter its functions by modulating the production of GMMs, which are capable of regulating homeostasis and the risk of disease.Complex interkingdom regulatory networks and crosstalk occur between the host, its gut microbiota, and its diet.Immortalized cancer cell lines grown in 2D monolayers differ genetically, metabolically, and phenotypically from in vivo cells. However, 3D IOs can mirror structural alterations, mutational signatures, and gene expression changes between patient and patient-derived organoids.IOs provide new opportunities to study how the gut microbiota , or its products, interact with intestinal epithelial cells. In this review, we discuss recent publications using IOs to study the nutrient–microbiome axis in gastrointestinal homeostasis and disease. We also highlight an array of novel approaches by which the nutrient–microbiota–gut epithelium triangle can be further understood and mechanisms governing gastrointestinal diseases better deciphered.