Project summary
Eating foods high in fat has been linked to damage to the lining of the gut and changes in the balance of bacteria that live there. Researchers believe these changes may play a role in the development of type 2 diabetes, alongside a mix of other risk factors, but we still don’t fully understand how or why.
Dr Natalie North and her team are investigating whether a natural molecule linked to a healthy gut can protect the body from the harmful effects of a high‑fat diet and help slow or prevent type 2 diabetes from developing.
Background to research
A high‑fat diet has been linked to damage the lining of the gut, the place where food is broken down and absorbed. When this lining is harmed, it can throw off the balance of gut bacteria (the microbiome), increase how much fat the body absorbs, and make it harder for the body to respond to insulin. Over time, this can lead to weight gain, fat building up in the liver, and a higher risk of type 2 diabetes.
Research shows that people with obesity or type 2 diabetes often have altered gut bacteria, but it’s still unclear why these changes happen or how they might contribute the development of type 2 diabetes develops .
Dr Natalie North’s team have discovered a new way the body may help protect the gut lining. They’ve found that blood vessel cells can release a molecule called uridine that ‘talks’ to the gut. Early lab studies suggest uridine can protect the gut lining from a high‑fat diet and in doing so support a healthier mix of gut bacteria. Now, the team will test whether uridine can help stop or slow the path toward type 2 diabetes.
Research aims
Dr Natalie North and the team will build on earlier findings using a two‑stage approach and cutting‑edge technology.
First, they’ll study whether transferring healthy gut bacteria from specially modified mice might protect against obesity and type 2 diabetes. Microbiomes containing uridine from these healthy mice will be transferred into mice with obesity, to see whether this improves gut health, weight and blood sugar levels.
Next, they’ll test the idea in human intestinal cells. By adding uridine, they’ll watch whether the gut lining becomes stronger, how gut bacteria is affected, and how this influences factors that drive the progression of type 2 diabetes. This ‘gut-on-a-chip’ model closely mimics how the human gut behaves and allows potential treatments to be tested safely before studies in people.
Potential benefit to people with diabetes
6.3 million people in the UK have a high risk of developing type 2 diabetes. Preventing or slowing the progression of the condition remains a major challenge.
While this research is still at an early stage, it will provide important evidence to determine whether targeting gut health using naturally occurring molecules could help reduce the risk of type 2 diabetes in the future and protect more people from its harm.
