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Updated: May 27, 2025

3D Culturing of Organoids from the Intestinal Villi Epithelium Undergoing Dedifferentiation
Published on: April 1, 2021
Intestinal crypt microbiota modulates intestinal stem cell turnover and tumorigenesis via indole acetic acid
Shuning Zhang1,2, Lihua Peng1, Shyamal Goswami1
1Laboratory for Microbiota-Host Interactions, The Center for Microbes, Development and Health, Shanghai Institute of Immunity and Infection-Chinese Academy of Sciences, Shanghai, China.
Abstract:
Intestinal crypts harbour a specific microbiota but whether and how these bacteria regulate intestinal stem cells (ISCs) or influence colorectal cancer (CRC) development is unclear. Here we screened crypt-resident bacteria in organoids and found that indole acetic acid (IAA) secreted by Acinetobacter radioresistens inhibits ISC turnover. A. radioresistens inhibited cellular proliferation in tumour slices from CRC patients and inhibited intestinal tumorigenesis and spheroid initiation in APCMin/+ mice. Targeted clearance of A. radioresistens from colonic crypts using bacteriophage increased EphB2 expression and consequently promoted cellular proliferation, ISC turnover and tumorigenesis in mouse models of CRC. The protective effects of A. radioresistens were abrogated upon deletion of trpC to prevent IAA production, or upon intestine-specific aryl hydrocarbon receptor (AhR) knockout, identifying an IAA-AhR-Wnt-β-catenin signalling axis that promotes ISC homeostasis. Our findings reveal a protective role for an intestinal crypt-resident microbiota member in tumorigenesis.
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