Adding to the growing body of research that proves our microbiome is a powerful ally in fighting disease, scientists have found that an easy-to-get nutrient in our food causes our guts to produce powerful insulin-regulating compounds.
For decades, medical science has been focused on developing treatments that are administered to patients from outside their own bodies. Now, however, more and more research is being focused on ways to marshal the team of microbes we have living in our guts to produce the compounds we need to fight disease. Earlier this year, for example, it was found that an antibiotic primarily used in veterinary medicine was able to convince the microbes in mouse guts to produce colonic acid, a life-extending compound.
Now, a team led by a researcher from Imperial College London has figured out another powerful way our gut microbes can help us out – this time by tamping down inflammation caused by a fatty diet, keeping our insulin response in check and, in turn, warding off diabetes.
When a person consistently eats a high fat diet, it can trigger chronic inflammation in the body through a combination of hormonal disruption, immune signaling, and cellular stress. That inflammation, in turn, can lead to insulin resistance, a state where our cells no longer properly respond to insulin, a hormone that allows the glucose in our blood to move into our cells for use as energy. This state can lead to type 2 diabetes where blood sugar levels spike and our pancreas struggles to pump out enough insulin to process it.
The researchers found that one of the chemicals involved in this cascade of negative effects is the immune-system protein IRAK4, which triggers inflammation in the presence of a high-fat diet as a sort of alarm bell. When that protein is expressed for an extended period of time, it leads to insulin resistance and diabetes.
The good news, however, is that the team also discovered a way to turn IRAK4 off.
Using mice, human cell models, and molecular target-screening, the scientists found that when the nutrient choline hits the gut, microbes convert it into a metabolite called trimethylamine (TMA). TMA, in turn, binds to IRAK4, blocks its activity, reduces inflammation, and restores insulin sensitivity. Choline is found in a wide range of foods but is particularly prominent in eggs, organ meats, fish, milk and dairy, as well as in beef, pork, and chicken.
"This flips the narrative," says lead study author Marc-Emmanuel 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."
The researchers not only showed that dietary choline could impact insulin sensitivity, but it also demonstrated that blocking IRAK4 either pharmacologically or through genetic alterations had the same effects on insulin resistance. This finding, the researchers believe, opens an entirely new way to treat diabetes brought on by high-fat diets either through dietary alterations or new types of medication.
"In view of the growing threat of diabetes worldwide and its devastating complications for the whole patient, including the brain and heart, a new solution is direly needed," said study co-author Peter Liu from the University of Ottowa Heart Institute. "Our team’s work connecting Western-style foods, TMA produced by the microbiome, and its effect on the immune switch IRAK4, may open entirely new ways to treat or prevent diabetes, a known risk factor for heart disease."
The research has been reported in the journal Nature Metabolism.
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