β-Elemene Rescues Radiation-Induced Enteritis by Orchestrating a Host-Microbiome Circuit That Fuels Epigenetic DNA...

Area of Science:

• Oncology
• Microbiology
• Molecular Biology

Background:

• Radiation-induced enteritis (RIE) is a significant radiotherapy side effect with limited treatment options.
• The gut microbiome influences radiation injury, but therapeutic manipulation is complex.

Purpose of the Study:

• To investigate the protective mechanism of β-elemene against RIE.
• To elucidate the synergistic interaction between β-elemene, host cells, and the gut microbiome.

Main Methods:

• Investigated β-elemene's effect on intestinal epithelial cells and gut microbiota in a RIE model.
• Analyzed host-microbe interactions, lactate metabolism, and epigenetic modifications.
• Identified key molecular players including MCT1, CD147, Lactobacillus gasseri, RBBP4, and EP300.

Main Results:

• β-elemene restored host cell lactate uptake by rescuing MCT1-CD147 interaction.
• β-elemene selectively increased Lactobacillus gasseri, boosting intestinal lactate production.
• Lactate initiated a cascade involving RBBP4 lactylation and EP300 recruitment, activating DNA repair genes.
• EP300 was identified as a lactyl-transferase, creating a positive feedback loop for DNA repair.

Conclusions:

• β-elemene employs a 'prime-and-fuel' strategy, coordinating host and microbial functions to combat RIE.
• This study reveals a novel drug-microbe-metabolite-epigenome axis for promoting tissue regeneration.