# Advanced human organoid-on-chip with physiological cellular complexity reveals bidirectional secretion patterns

## TL;DR

A new human intestinal organoid-on-chip model reveals how different cell types and stimuli influence immune regulator secretion patterns.

## Contribution

Development of a human intestinal organoid-on-chip model with adjustable cell composition to study bidirectional secretion and barrier function.

## Key findings

- The organoid-on-chip model shows asymmetric, bidirectional cytokine secretion depending on epithelial cell type.
- Secretion patterns are sensitive to inflammatory stimuli, bacteria, and dietary antigens.
- The model offers a platform to study gut barrier function under physiological and disease conditions.

## Abstract

Intestinal epithelial cells are essential for maintaining gut homeostasis, serving as a physical barrier separating luminal content from the immune compartment. They are crucial for balancing tolerance to commensal and protection from pathogenic bacteria and dietary antigens by the asymmetric secretion of immune regulators. To understand how different epithelial cell types and external stimuli shape this secretion pattern, we established and characterized a human intestinal organoid-on-chip (OoC) model. OoCs were used to evaluate barrier integrity and cell type-dependent expression profiles by RNA-sequencing and microscopy. Secretome analysis revealed asymmetric bidirectional secretion and a cell type-dependent response to LPS, flagellin, gliadin, and cytokines. In summary, we have developed an OoC model using human intestinal cells, offering a cutting-edge platform to study barrier function under physiological and pathophysiological conditions. This versatile tool holds significant promise for advancing our understanding of epithelial cells in innate immunity and driving the development of personalized therapeutic strategies.

•Human intestinal organoid-on-chip model for barrier and secretion studies•Adjustable crypt-like or multi-lineage epithelial cell-type composition•Asymmetric, bidirectional cytokine secretion depends on epithelial cell type•Secretion is sensitive to inflammatory stimuli, bacteria, and dietary antigens

Human intestinal organoid-on-chip model for barrier and secretion studies

Adjustable crypt-like or multi-lineage epithelial cell-type composition

Asymmetric, bidirectional cytokine secretion depends on epithelial cell type

Secretion is sensitive to inflammatory stimuli, bacteria, and dietary antigens

Immunology; biological sciences; biomedical engineering