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Updated: Mar 20, 2026
07:46
Three-Dimensional Culture of Murine Colonic Crypts to Study Intestinal Stem Cell Function Ex Vivo
Published on: October 11, 2022
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The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites
Gerard E Kaiko1, Stacy H Ryu1, Olivia I Koues1
1Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell
|June 7, 2016
Summary
Butyrate, a gut microbe metabolite, inhibits intestinal stem cell proliferation. Mammalian gut structure creates a metabolic barrier, preventing butyrate from reaching stem cells during normal conditions, thus protecting their growth.
Area of Science:
- Gastroenterology
- Microbiome Research
- Stem Cell Biology
Background:
- Mammalian intestinal crypts harbor stem/progenitor cells.
- Microbial metabolites can influence stem cell activity.
- Butyrate is a key bacterial metabolite in the gut.
Purpose of the Study:
- To investigate the effect of butyrate on intestinal stem/progenitor cell proliferation.
- To understand the role of gut architecture in modulating stem cell response to metabolites.
Main Methods:
- Unbiased screening to identify metabolites affecting stem cell proliferation.
- In vivo exposure of stem/progenitor cells to butyrate.
- Analysis of the mechanism involving the transcription factor Foxo3.
Main Results:
- Butyrate was identified as a potent inhibitor of intestinal stem/progenitor proliferation at physiological concentrations.
- Differentiated colonocytes metabolize butyrate during homeostasis, creating a barrier.
- Exposure to butyrate inhibited proliferation and delayed wound repair, mediated by Foxo3.
Conclusions:
- Mammalian crypt architecture protects stem cell proliferation via a metabolic barrier formed by colonocytes consuming butyrate.
- This highlights the interplay between host anatomy and microbiome metabolism in regulating intestinal stem cells.
- Further research is needed to explore this host-microbiome interaction.
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