Detecting host responses to microbial stimulation using primary epithelial organoids.

Area of Science:

• Microbiology
• Gastroenterology
• Cell Biology

Background:

• The intestinal epithelium interacts with luminal microbes.
• Cancer-derived cell lines (e.g., Caco-2) are traditionally used to study these interactions.
• It remains unclear if these cell lines accurately represent normal epithelial responses and strain-specific microbial effects.

Purpose of the Study:

• To investigate microbial responses in normal intestinal epithelium using organoids.
• To compare responses between healthy organoids and Caco-2 cell lines.
• To identify common and strain-specific microbial interactions.

Main Methods:

• Derived intestinal organoids from healthy individuals (n=9).
• Cultured organoids on a laminin matrix to induce differentiation and apical exposure.
• Exposed differentiated organoids to probiotic bacterial strains (BB-12®, LGG®, DSM33361, Bif195).
• Performed parallel experiments using Caco-2 cell lines.

Main Results:

• Healthy intestinal organoids exhibited robust acute responses to various probiotic strains.
• Both common and strain-specific responses were observed across individuals.
• Caco-2 cell lines showed no acute response to the tested probiotics.
• Organoid models revealed individual variability in microbial responses.

Conclusions:

• Primary intestinal organoids from healthy individuals are a valuable model for studying host-microbe interactions.
• Organoids provide a more accurate representation of normal epithelial responses compared to Caco-2 cells.
• This approach enhances understanding of individual variations in host-microbe dynamics and microbial strain specificity.