Researchers have identified an unexpected natural compound that may counter insulin resistance and type 2 diabetes: trimethylamine (TMA), a metabolite produced by gut microbes from dietary choline.
A study in Nature Metabolism shows TMA can interrupt a key immune pathway and support healthier blood sugar control. The discovery builds on work that began 20 years ago, when Imperial College London and University of Louvain scientist Patrice Cani found that high-fat diets allow bacterial components to cross into the body and ignite inflammation. This immune response was later shown to play a direct role in insulin resistance. Once controversial, the idea is now widely accepted.
In 2025, teams from the University of Louvain and Imperial College London reported TMA can help improve blood sugar regulation. The effect centers on TMA’s interaction with IRAK4, a protein that regulates immune activity. Under long-term high-fat intake, IRAK4 becomes overstimulated and drives chronic inflammation, which contributes to insulin resistance.
Using human cell cultures, animal studies and molecular screening tools, the researchers showed TMA can attach to IRAK4 and reduce its activity. Dampening this pathway lowers inflammation and restores the body’s ability to respond to insulin. TMA also protected mice from sepsis-related death by weakening overwhelming inflammatory responses.
“This flips the narrative,” said researcher Marc-Emmanuel Dumas. “It’s a new way of thinking about how the microbiome influences our health.”
“This shows how nutrition and our gut microbes can work together by producing molecules that fight inflammation and improve metabolic health,” added Cani.
With more than 500 million people worldwide living with diabetes, identifying TMA as a microbial signal that shapes immune responses introduces a promising avenue for future treatment.
For more information, visit nature.com.
