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Gut Microbe Molecule TMA Inhibits IRAK4, Easing Diet-Driven Inflammation in Diabetes Models

The Nature Metabolism study spotlights IRAK4 as a drug target, with microbiome-informed nutrition proposed for future testing.

Overview

  • TMA, a metabolite produced from dietary choline, directly binds the immune kinase IRAK4 to curb fat-induced inflammation and restore insulin sensitivity in preclinical experiments.
  • Evidence spans molecular target screening, human cell models, and mouse studies, with IRAK4 genetic deletion or pharmacologic inhibition mirroring TMA’s metabolic benefits.
  • In mice fed high-fat diets, boosting choline intake raised circulating TMA roughly twentyfold and was linked with improved inflammatory and glycaemic readouts.
  • A single TMA dose improved survival in a mouse model of LPS-induced sepsis, indicating broader anti-inflammatory effects beyond glucose control.
  • The international team from Imperial College London, UCLouvain, and the University of Ottawa Heart Institute reports a translational path via IRAK4-directed drugs or diet–microbiome strategies, though human trials have yet to begin.