Scientists have discovered a way to combat the inflammation caused by a high-fat diet that leads to the insulin resistance seen in diabetes.
The international team say it is a major breakthrough in the battle against Type 2 diabetes and paves the way for the development of new drugs and treatments. Their message is that what we eat shapes our microbes and some of the molecules they produce can actually protect us from diabetes.
More than 500 million people worldwide are affected by diabetes, with the Middle East a region where the condition is particularly prevalent. More than four in 10 people with diabetes are unaware they are living with the condition, a study has shown.
Diabetes poses a significant health threat and economic challenge to the Middle East and North Africa, a report published last month found. That could cost $1.5 trillion a year by 2050 without urgent intervention. The study carried out by the University of Birmingham Dubai, in collaboration with the World Health Organisation, found that diabetes cost the region $639 billion in 2023 – and the economic burden is expected to increase.
The study, published in the Nature Metabolism journal, focused on bacteria formed in the gut that can help improve blood sugar control. The researchers, from Imperial College London, the University of Louvain and the University of Ottawa Heart Institute uncovered a surprising ally in the fight against diabetes – a microbial metabolite called trimethylamine (TMA). Microbial metabolites are chemical compounds produced by bacteria or fungi as they process substances so they can be used in the body.
Prof Patrice Cani, of Imperial College London, discovered 20 years ago that a high fat diet leads to compounds in the body that activate the immune system and trigger inflammation, eventually causing insulin resistance.
Now his team have uncovered how to counter the process using TMA – which is found in foods high in the nutrient choline, such as eggs, liver and seafood – as a natural inhibitor to a protein that triggers inflammation when exposed to a high fat diet.
The protein IRAK4 can overreact when constantly overloaded and drives insulin resistance. By combining human cell models, mouse studies and molecular-target screening, the team discovered that TMA can bind directly to IRAK4 and block its activity. In effect, it can reprogramme the negative metabolic response to poor diet.
“This shows how nutrition and our gut microbes can work together by producing molecules that fight inflammation and improve metabolic health,” Prof Cani said.
Genetically deleting IRAK4, or blocking it using drugs, can create the same affect, they believe, which gives them a target for therapy. “This flips the narrative,” said Prof Marc-Emmanuel Dumas, also from Imperial College London. “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.”
