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Microbe-Made Molecule Disarms IRAK4, Improving Glucose Control in Preclinical Study

The study identifies direct IRAK4 inhibition by gut-derived trimethylamine as a preclinical route to better glucose control.

Overview

  • Published in Nature Metabolism, the work was led by researchers at Imperial College London with colleagues at UCLouvain and the University of Ottawa Heart Institute.
  • Trimethylamine (TMA), produced by gut bacteria from dietary choline found in foods such as eggs, liver, and seafood, was pinpointed as the active metabolite.
  • Experiments in human cell models and mice showed that TMA binds to the immune kinase IRAK4, dampens fat-induced inflammatory signaling, and restores insulin sensitivity.
  • Genetic deletion of IRAK4 or pharmacological blockade reproduced TMA’s beneficial effects, highlighting IRAK4 as a viable drug target for metabolic disease.
  • The authors report protection against sepsis-related death in mice, while emphasizing that the findings are preclinical and will require human safety and efficacy studies before translation to therapies.