Role of gut microbiota in the development of Type II Diabetes
Diabetes mellitus (DM) is defined as a set of combined metabolic diseases where high blood sugar levels are a predominant common factor. Some of the associated symptoms include increased urination (polyuria), thirst (polydipsia) and hunger (polyphagia), which is why DM is known as the disease of the 3Ps. DM is divided in three categories depending on its origin: Type I Diabetes (which results from pancreas failure), Type II Diabetes (due to insulin resistance) and Gestational Diabetes (when pregnant women without a previous history of diabetes develop the condition, which usually resolves after giving birth).
What is Type II Diabetes and why is it an issue?
Type II Diabetes (T2D) is a complex metabolic disorder often associated with excessive body weight. It is a major source of concern in Western and developing countries as it was estimated in 2015 that over 350 millions individuals worldwide were affected [source diabetes.org.uk] and is predicted to affect up to 5 millions individuals in the UK by 2025. Currently T2D and its associated complications represent approximately 10% of the NHS budget. Some of these complications involve amputations, blindness, kidney failure, nerve damage and stroke. Although a number of medications are available to limit these damages, it does not have a cure.
What are the causes of T2D?
T2D results from a state of insulin resistance, that is when the body fails to respond to normal insulin levels, which can be combined with an insufficient insulin secretion. The origins of these deficiencies are the result of a complex interplay between genes and lifestyle. Some known factors contributing to increase the risk of development of T2D are obesity (body mass index > 30), stress, lack of physical activity, urbanisation and poor diet. Underlying these factors, there is increasing evidence that gut microbiota and their interaction with human metabolism may play a role in its development. For example, many studies have demonstrated that the gut microbial ecosystem was altered in patients suffering from T2D. However, it remains unclear whether these changes play a causal role in the development of this disease. Thus, the overall aim of this project is to explore the links between the gut microbiota and the pathophysiological processes leading to T2D. In particular, we will question the impact of gut bacteria in early life on the altered endogenous energy pathways associated with the development of insulin resistance processes.
Our main objectives
1-To characterise the gut microbial differences between diabetic and non-diabetic individuals in an animal model of T2D.
2-To identify the key metabolic pathways influenced by the diabetic maternal gut microbiota.
3-To understand the perturbations of the energy pathways resulting from foetal exposure to a diabetic microbiota.