Creating a More Perfect Union: Modeling Intestinal Bacteria-Epithelial Interactions Using Organoids

Intestinal organoids have become indispensable tools for many gastrointestinal researchers, advancing their studies of nontransformed intestinal epithelial cells, and their roles in an array of diseases, including inflammatory bowel disease and colon cancer. In many cases. these diseases, as well as many enteric infections, reflect pathogenic interactions between bacteria and the gut epithelium. The complexity of studying this microbe-epithelial interface in vivo has led to significant focus on modeling this crosstalk using organoid models. Considering how quickly the organoid field is advancing, it can be difficult to keep up to date with the latest techniques, as well as their respective strengths and weaknesses. This review addresses the advantages of using organoids derived from adult stem cells and the recently identified differences that biopsy location and patient age can have on organoids and their interactions with microbes. Several approaches to introducing bacteria in a relevant (apical) manner (ie, microinjecting 3-dimensional spheroids, polarity-reversed organoids, and 2-dimensional monolayers) also are addressed, as are the key readouts that can be obtained using these models. Lastly, the potential for new approaches, such as air-liquid interface, to facilitate studying bacterial interactions with important but understudied epithelial subsets such as goblet cells and their products, is evaluated.

Automated summary

Intestinal organoids play a crucial role in gastrointestinal research, particularly in studying nontransformed intestinal epithelial cells and their involvement in diseases like inflammatory bowel disease and colon cancer. Research on the advantages of using organoids derived from adult stem cells, as well as the impact of biopsy location and patient age on organoids and their interactions with microbes, has made significant progress. Various methods of introducing bacteria in a relevant manner and assessing key outputs using these models have also been addressed.