A microbiota-IPA axis facilitates intestinal stem cell-mediated regeneration in colitis through a Hopx-associated...

Area of Science:

• Gastroenterology
• Microbiology
• Stem Cell Biology

Background:

• The gut microbiota is vital for intestinal stem cell (ISC) homeostasis and epithelial barrier function.
• Blautia coccoides (B. coccoides) is found to be significantly reduced in inflammatory bowel disease (IBD) patients and DSS-induced colitis models.

Purpose of the Study:

• To investigate the role of B. coccoides in intestinal epithelial repair and identify underlying molecular mechanisms.
• To explore the potential of microbiota-derived metabolites as therapeutic agents for IBD.

Main Methods:

• Integrated analysis of RNA sequencing, metabolomic profiling, and ISC lineage tracing in mucosal injury models.
• Utilized engineered Escherichia coli to assess the function of bacterial enzymes in metabolite production.

Main Results:

• B. coccoides colonization increases beta-hydroxybutyrate (BHB) in intestinal epithelial cells (IECs), activating reserve ISCs and promoting LGR5+ ISC pool regeneration.
• B. coccoides-derived indole-3-lactic acid (ILA) is converted to indole-3-propionic acid (IPA) by other commensals, stimulating BHB synthesis and mucosal healing.
• Dietary tryptophan and bacterial fldH activity are essential for ILA/IPA generation and epithelial repair.

Conclusions:

• A novel microbiota-metabolite-ISC regulatory axis is identified, crucial for epithelial regeneration.
• B. coccoides and its metabolites represent potential therapeutic targets for IBD and intestinal barrier dysfunction.