Microbiota and type 2 diabetes
Over the past 15 years, considerable effort has been directed toward clarifying how the gut microbiota associates with obesity and cardiometabolic diseases. Obesity results from an imbalance between energy intake and energy expenditure and is a well-established risk factor for type 2 diabetes. However, not all individuals with obesity develop type 2 diabetes and additional factors are known to play a role in this disease. We and others have shown that the gut microbiota is altered in subjects with type 2 diabetes and that the microbiome may have predictive capacity for type 2 diabetes.
One major challenge in the microbiome field is to determine whether the microbiota contributes to the disease or whether the altered microbiota is simply the result of the disease itself or treatments for the disease. The following points provide evidence supporting a role for the gut microbiota in the development of type 2 diabetes.
- We have shown that individuals with prediabetes (particularly those with impaired glucose tolerance) have an altered gut microbiota. One consistent feature of the microbiota in individuals with prediabetes/type 2 diabetes is low abundance of butyrate-producing bacteria.
- We have shown that diabetes phenotypes can be transferred by colonizing germ-free mice with fecal microbiota from humans with type 2 diabetes.
- Our collaborator Max Nieuwdorp has shown that transfer of fecal microbiota from lean healthy individuals to individuals with the metabolic syndrome can improve insulin sensitivity.
- We and others have identified a number of microbially produced metabolites (such as branched-chain amino acids, imidazole propionate, and secondary bile acids) that are associated with type 2 diabetes.
Our major focus is to use the microbiota to improve stratification of individuals with prediabetes and type 2 diabetes and design personalized microbiome-based treatments. To achieve this goal, it is important to increase our mechanistic insight into how the gut microbiota can contribute to insulin resistance and type 2 diabetes.
"Hope for a drug against type 2 diabetes"
A film produced by Knut & Alice Wallenberg Foundation.
Want to know more?
- Gut metagenome in European women with normal, impaired and diabetic glucose control, Nature (2013)
- Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug, Nature Medicine (2017)
- The gut microbiota in prediabetes and diabetes: A population-based cross-sectional study, Cell Metabolism (2020)
- Microbially produced imidazole propionate impairs insulin signaling through mTORC1, Cell (2018)