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An international research team has uncovered a surprising ally in the fight against insulin resistance and type 2 diabetes: a microbial metabolite called trimethylamine (TMA). Published in Nature Metabolism, the study reveals that TMA, produced by gut bacteria from dietary choline, can block a key immune pathway and improve blood sugar control.

The study was led by Professor Marc-Emmanuel Dumas at Imperial College London & CNRS together with Prof. Patrice Cani (Imperial & University of Louvain, UCLouvain), Dr. Dominique Gauguier (Imperial & INSERM, Paris) and Prof. Peter Liu (University of Ottawa Heart Institute).

Discovery of inflammation’s role in diabetes

This major breakthrough has its roots 20 years earlier. During his postdoctoral research, Patrice Cani discovered that a high-fat diet leads to the presence of bacterial components in the body, which activates the immune system and triggers inflammation, eventually causing insulin resistance in diabetic individuals. Considered far-fetched in 2005, this finding is now well established and widely accepted by scientists.

In 2025, researchers from University of Louvain and Imperial College London finally uncovered how to counter this process. They observed that TMA, produced by gut bacteria from a natural nutrient, dietary choline, found in certain foods can improve blood-sugar control.

How TMA blocks harmful immune response

How? By acting as a natural inhibitor of the protein IRAK4, a key component of the immune system. Normally, when exposed to a high-fat diet, IRAK4 sounds the alarm and triggers inflammation to signal dietary imbalance.

The problem? With constant overload (as seen in type 2 diabetes), IRAK4 overreacts, causing cascading inflammation that drives insulin resistance.

By combining human cell models, mouse studies, and molecular-target screening, scientists discovered that TMA can bind directly to IRAK4 and block its activity. The direct effect is a reduction in fat-induced inflammation and a restoration of insulin sensitivity. In essence, it reprograms the negative metabolic responses caused by poor diet. Even more striking: the molecule can prevent sepsis-induced mortality in mice by blocking widespread inflammation.

Implications for diabetes treatment

"This shows how nutrition and our gut microbes can work together by producing molecules that fight inflammation and improve metabolic health," said Prof. Patrice Cani, co-senior author, University of Louvain, Belgium and visiting professor at Imperial College London.

The team also observed that genetically deleting IRAK4 or blocking it pharmacologically reproduced the beneficial effects of the bacterial metabolite. This opens new therapeutic avenues for diabetes, using a target, IRAK4, that is already validated within the pharmaceutical industry.

"This flips the narrative," said Prof. Dumas. "We’ve shown that a molecule from our gut microbes can actually protect against the harmful effects of a poor diet through a new mechanism. It’s a new way of thinking about how the microbiome influences our health."

With more than 500 million people worldwide affected by diabetes, identifying TMA as a microbial signal that modulates immunity could pave the way for new treatments. Nutritional strategies or drugs designed to boost TMA production may offer a new approach to combating insulin resistance and its complications.

"What we eat shapes our microbes and some of their molecules can protect us from diabetes. That’s nutrition in action," said University of Louvain, Prof. Cani.

More information: ‘Inhibition of IRAK4 by microbial trimethylamine blunts metabolic inflammation and ameliorates glycemic control’, Nature Metabolism (2025). DOI: 10.1038/s42255-025-01413-8

Citation: Microbial molecule that disarms inflammation discovered, offering new diabetes treatment strategy (2025, December 8) retrieved 8 December 2025 from https://medicalxpress.com/news/2025-12-microbial-molecule-inflammation-diabetes-treatment.html

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