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Author Spotlight: Gut Microbiome-Lung Tissue Communication Through Short-Chain Fatty Acid Analysis
Published on: June 21, 2024
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Histone Deacetylase Inhibition by Gut Microbe-Generated Short-Chain Fatty Acids Entrains Intestinal Epithelial
Jibraan A Fawad1, Deborah H Luzader1, Gabriel F Hanson1
1Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Virginia, Charlottesville, Virginia.
Gastroenterology
|August 7, 2022
Summary
Gut microbes influence our internal body clock through metabolites like short-chain fatty acids (SCFAs). These SCFAs, via an epigenetic mechanism involving histone deacetylase inhibitors, help regulate intestinal epithelial rhythms and overall gut health.
Area of Science:
- Chronobiology
- Microbiome research
- Epigenetics
Background:
- The circadian clock regulates daily rhythms in the gut epithelium and microbiota.
- Gut microbial metabolites reciprocally influence epithelial circadian rhythms.
- An epigenetic mechanism mediates these microbe-epithelial interactions.
Purpose of the Study:
- To investigate the impact of gut microbial metabolites on intestinal epithelial timekeeping.
- To elucidate the epigenetic mechanisms involved in this interaction.
- To identify specific microbial metabolites that phase-shift circadian rhythms.
Main Methods:
- Culturing murine enteroids with microbial supernatants.
- Measuring circadian oscillations (PER2, Bmal1) in response to metabolites.
- Utilizing machine learning for metabolomics analysis to identify phase-shifting compounds.
- Testing the effects of short-chain fatty acids (SCFAs) and histone deacetylase (HDAC) inhibitors.
Main Results:
- Specific gut microbial species' supernatants induced significant phase shifts in circadian rhythms.
- Short-chain fatty acids (SCFAs) were identified as key phase-shifting metabolites.
- SCFAs shifted murine enteroid circadian rhythms by a median of 6.2 hours.
- HDAC inhibitors mimicked SCFA effects, and HDAC3 was implicated in mediating butyrate's impact.
- Findings were validated in human intestinal cells.
Conclusions:
- Gut microbe-derived SCFAs entrain intestinal epithelial circadian rhythms via an HDAC-dependent epigenetic mechanism.
- This highlights the intricate interplay between the microbiome, epigenetics, and circadian regulation of gut homeostasis.
- Understanding this mechanism is crucial for maintaining intestinal health.
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