An international research team has made a groundbreaking discovery that could revolutionize the treatment of type 2 diabetes. Led by Professor Marc-Emmanuel Dumas at Imperial College London and CNRS, alongside Prof. Patrice Cani from the University of Louvain and Imperial, Dr. Dominique Gauguier from INSERM, Paris, and Prof. Peter Liu from the University of Ottawa Heart Institute, the team has identified a microbial metabolite, trimethylamine (TMA), that can significantly reduce insulin resistance. The study, published in Nature Metabolism, reveals that TMA, produced by gut bacteria from dietary choline, can block a critical immune pathway and improve blood sugar control.
This breakthrough is rooted in research dating back 20 years. During his postdoctoral studies, Prof. Cani discovered that a high-fat diet leads to the presence of bacterial components in the body, which activate the immune system and trigger inflammation, eventually causing insulin resistance. Initially considered speculative in 2005, this finding is now well-established and widely accepted among scientists.
The Mechanism Behind the Discovery
In 2025, researchers from the University of Louvain and Imperial College London unraveled the mechanism by which TMA counters this process. They found that TMA acts as a natural inhibitor of the protein IRAK4, a key component of the immune system. Under normal circumstances, IRAK4 responds to a high-fat diet by triggering inflammation to signal dietary imbalance. However, in cases of constant overload, as seen in type 2 diabetes, IRAK4 overreacts, causing inflammation that drives insulin resistance.
By employing human cell models, mouse studies, and molecular-target screening, scientists discovered that TMA can bind directly to IRAK4 and block its activity. This results in a reduction of fat-induced inflammation and a restoration of insulin sensitivity. Remarkably, the molecule can also prevent sepsis-induced mortality in mice by blocking widespread inflammation.
“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.
Implications for Future Treatments
The research team also observed that genetically deleting IRAK4 or blocking it pharmacologically reproduced the beneficial effects of the bacterial metabolite. This discovery opens new therapeutic avenues for diabetes, targeting IRAK4, a protein 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 over 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 novel 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 Prof. Cani.
Global Collaboration and Future Directions
This research was made possible through international collaborations across Europe and North America, involving institutions in Belgium, Canada, Australia, France, Italy, and Spain. The work was supported by numerous European (ERC, FEDER) and national (MRC, Wellcome Trust, ANR, FNRS, EOS, WELRi, ARC) funding sources.
The discovery of TMA’s role in modulating immune responses and improving metabolic health represents a significant step forward in understanding the complex interactions between diet, gut microbiota, and chronic diseases. As researchers continue to explore the potential of microbial metabolites, the hope is to develop new, effective treatments for diabetes that harness the natural power of the human microbiome.
Moving forward, the team aims to conduct clinical trials to further investigate TMA’s therapeutic potential in humans and explore how dietary interventions could optimize gut microbiota to enhance health outcomes. This innovative approach could redefine the landscape of diabetes treatment, offering new hope to millions worldwide.
