A microbiota-IPA axis facilitates intestinal stem cell-mediated regeneration in colitis through a Hopx-associated program - PubMed
4 hours ago
- #microbiota
- #IBD
- #intestinal stem cells
- The gut microbiota is crucial for intestinal stem cell (ISC) homeostasis and epithelial barrier integrity.
- Blautia coccoides (B. coccoides) is significantly reduced in IBD patients and DSS-induced colitis mice.
- B. coccoides colonization enhances β-hydroxybutyrate (BHB) production in intestinal epithelial cells (IECs).
- BHB activates HOPX+ reserve ISCs and promotes regeneration of the LGR5+ ISC pool, aiding epithelial repair.
- B. coccoides-derived indole-3-lactic acid (ILA) is converted into indole-3-propionic acid (IPA) by commensal bacteria.
- IPA stimulates IEC BHB synthesis, facilitating mucosal healing.
- Dietary tryptophan (Trp) and bacterial fldH activity are essential for ILA/IPA generation and mucosal healing.
- The study reveals a microbiota-metabolite-ISC regulatory axis critical for epithelial regeneration.
- Findings propose novel metabolite-based therapeutic strategies for IBD and related intestinal disorders.