# Wnt/β-Catenin Pathway Activation Confers Fumonisin B1 Tolerance in Chicken Intestinal Organoid Monolayers by Enhancing Intestinal Stem Cell Function

## TL;DR

Chickens resist the mycotoxin fumonisin B1 by activating a pathway that boosts intestinal stem cell function and epithelial regeneration.

## Contribution

A 2D chicken intestinal organoid model reveals FB1 resistance in poultry via Wnt/β-catenin pathway activation and stem cell enhancement.

## Key findings

- FB1 does not disrupt chicken intestinal monolayer resistance or tight junction gene expression.
- FB1 activates the Wnt/β-catenin pathway to enhance intestinal stem cell function in chickens.
- Chicken intestinal organoid monolayers show low susceptibility to FB1 compared to porcine models.

## Abstract

Fumonisin B1 (FB1), a common mycotoxin in moldy grains/feeds, harms livestock and threatens food safety, but poultry’s FB1 tolerance mechanism remains unclear. Traditional 3D chicken organoid models cannot simulate epithelial monolayer–toxin interaction, limiting FB1-intestinal crosstalk studies. This study used a 2D chicken intestinal organoid monolayer model to explore poultry’s FB1 resistance mechanisms. Unlike porcine models, FB1 did not reduce the monolayer’s transepithelial electrical resistance, disrupt tight junction gene expression, or fluctuate inflammatory factor levels in chickens. Mechanistically, FB1 activates the Wnt/β-catenin pathway to enhance intestinal stem cell function and promote epithelial regeneration, boosting chickens’ FB1 resistance. The findings reveal a FB1 tolerance strategy in poultry and provide new insights for mycotoxin control.

Fumonisin B1 (FB1) is a prevalent mycotoxin in moldy grains and feeds, highly toxic to livestock and compromising product quality while threatening food safety. Poultry exhibit low susceptibility to FB1, but the underlying tolerance mechanisms remain unclear. Traditional 3D chicken intestinal organoid models cannot simulate direct interaction between the epithelial monolayer and FB1, limiting the study of FB1–chicken intestinal crosstalk. Here, we established a 2D chicken intestinal organoid monolayer model, derived from intestinal crypts of 18-day-old specific pathogen-free chicken embryos, to systematically explore poultry’s resistance mechanisms against FB1. Using this model, we compared FB1-induced effects with those in a porcine intestinal epithelial cell model. Results showed that FB1 exposure did not reduce transepithelial electrical resistance, induce abnormal expression of tight junction genes, or cause significant fluctuations in inflammatory factor levels in chicken intestinal organoid monolayers. Mechanistically, FB1 enhances chicken intestinal stem cell function by activating the Wnt/β-catenin pathway, thereby promoting epithelial regeneration and renewal to increase FB1 resistance and decrease toxin sensitivity in chickens. This study reveals a strategy for enhancing FB1 tolerance in poultry by promoting intestinal stem cell function, providing a new perspective for developing mycotoxin prevention and control strategies.