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High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide
Woongjae Yoo1,2, Jacob K Zieba1,2, Nora J Foegeding2,2
1Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Science (New York, N.Y.)
|August 13, 2021
Summary
A high-fat diet alters gut bacteria
Area of Science:
- Microbiology
- Gut Microbiome
- Metabolic Disease
Background:
- Western diets high in choline promote cardiovascular disease via gut microbiota metabolism.
- Choline is converted to trimethylamine (TMA), a precursor to harmful metabolites.
- Diet-induced changes in intestinal physiology's impact on microbial metabolism are unknown.
Purpose of the Study:
- To investigate how high-fat diets alter intestinal physiology.
- To determine if these changes affect gut microbial choline metabolism.
- To link these alterations to cardiovascular disease risk.
Main Methods:
- Used a mouse model of diet-induced obesity.
- Analyzed colonic epithelial mitochondrial bioenergetics.
- Measured oxygen and nitrate bioavailability in the gut lumen.
- Assessed *Escherichia coli* choline catabolism.
- Quantified circulating trimethylamine N-oxide (TMAO) levels.
Main Results:
- High-fat diet impaired colonic epithelial mitochondrial function.
- This led to increased luminal oxygen and nitrate availability.
- *Escherichia coli* enhanced its respiration-dependent choline catabolism.
- Circulating TMAO levels were elevated.
Conclusions:
- Diet-induced changes in intestinal physiology can enhance gut microbial metabolism.
- High-fat diets promote TMAO production by increasing *E. coli* choline catabolism.
- This mechanism links Western diets to cardiovascular disease risk.
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