Gut Microbe-Derived Trimethylamine Shapes Circadian Rhythms Through the Host Receptor TAAR5

Nov 24, 2025bioRxiv : the preprint server for biology

Gut Microbe Chemical Trimethylamine May Influence Body Clock Through a Specific Host Receptor

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Abstract

Mice lacking the host receptor for trimethylamine (TMA) show altered circadian rhythms and metabolic changes.

  • Elevated levels of the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) are linked to cardiometabolic disease risk.
  • Dietary choline is converted by gut bacteria into TMA, which is then oxidized by the host to produce TMAO.
  • Mice without the TMA receptor exhibit changes in gene expression related to circadian rhythms and metabolism.
  • Genetic alterations that prevent TMA production or its oxidation also lead to fluctuations in circadian rhythms.
  • These findings suggest a connection between gut bacteria, host metabolism, and circadian regulation.

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