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

Area of Science:

• Gastroenterology and Microbiology
• Biomedical Engineering
• Cell Biology

Background:

• Intestinal organoids are crucial for studying gut epithelial cells and diseases like inflammatory bowel disease and colon cancer.
• Understanding microbe-epithelial interactions is key, as many gut diseases and infections involve bacteria.
• In vivo studies of the microbe-epithelial interface are complex, driving the development of organoid models.

Purpose of the Study:

• To review current organoid techniques for studying microbe-epithelial interactions.
• To highlight the strengths and weaknesses of various organoid modeling approaches.
• To discuss the impact of biopsy location and patient age on organoid-microbe interactions.

Main Methods:

• Review of existing literature on intestinal organoid models.
• Analysis of techniques for introducing bacteria to organoids (e.g., microinjection, polarity-reversed organoids, 2D monolayers).
• Evaluation of novel methods like air-liquid interface for studying specific epithelial cell types.

Main Results:

• Adult stem cell-derived organoids offer advantages for studying gut epithelium.
• Biopsy location and patient age significantly influence organoid characteristics and microbial interactions.
• Various methods allow for apical introduction of bacteria, enabling relevant modeling.

Conclusions:

• Organoid models provide powerful tools for dissecting complex microbe-epithelial interactions in the gut.
• Emerging techniques like air-liquid interface hold promise for studying underrepresented epithelial cell subsets.
• This review synthesizes current knowledge and future directions in gut organoid research for infectious and inflammatory diseases.