Currently, scientists think the major contributors to insulin resistance are excess weight and physical inactivity, yet ground-breaking new research, with leading Danish authors from Technical University of Denmark and Copenhagen University published in Nature have discovered that specific gut bacteria can cause insulin resistance, which confers an increased risk of health disorders like type 2 diabetes.
“This study is the first to show that there is a causal link between specific gut bacteria and insulin resistance. It also explains why pre-diabetic individuals often have elevated levels of branched chain amino acids (BCAA) and a number of other metabolites in the blood, says Henrik Bjørn Nielsen, lead author from the Technical University of Denmark, who together with Helle Krogh Pedersen and Valborg Gudmundsdóttir did the analysis.
“The study represents very significant medical and technical advances, and it is the first study to integrate serum metabolome, microbiome and clinical data in a three-pronged analysis. The analysis weight the impact of the different bacterial species, and this enabled us to identify the species that was most important for insulin resistance. Interestingly, this species caused insulin resistance only three weeks after it was fed to mice” adds Henrik Bjørn Nielsen.
In the Danish study of 277 non-diabetic individuals and 75 type 2 diabetic patients, there was a close collaboration between the Danish researchers and researchers from the EU funded MetaHit consortium. They monitored the concentrations of more than 1200 metabolites in blood and did advanced DNA-based studies of hundreds of bacteria in the human intestinal tract to explore if certain imbalances in gut microbiota are involved in the causation of common metabolic and cardiovascular disorders.
The researchers observed that people who had a decreased capacity of insulin action, and therefore were insulin resistant, had elevated blood levels of a subgroup of amino acids called branched-chain amino acids (BCAAs). Importantly, the rise of BCAAs levels in blood was related to specific changes in the gut microbiota composition and function.
The main drivers behind the gut bacterial biosynthesis of BCAAs turned out to be the two bacteria Prevotella copri and Bacteroides vulgatus. To test mechanistically if gut bacteria were a true cause of insulin resistance, the researchers fed mice with the Prevotella copri bacteria for 3 weeks. Compared with sham fed mice the Prevotella copi fed mice developed increased blood levels of BCAAs, insulin resistance and intolerance to glucose.
“We show that specific imbalances in the gut microbiota are essential contributors to insulin resistance, a forerunner state of widespread disorders like type 2 diabetes, hypertension and atherosclerotic cardiovascular diseases, which are in epidemic growth,” says Professor Oluf Pedersen, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, and senior lead author of the paper.
“Most people with insulin resistance do not know that they have it. However, it is known that the majority of overweight and obese individuals are insulin resistant and it is well known that dietary shifts to less calorie-dense eating and increased daily intake of any kind of vegetables and less intake of food rich in animal fat tend to normalize imbalances of gut microbiota and simultaneously improve insulin sensitivity of the host,” adds Oluf Pedersen.
“Even though this study shows that the microbiome plays an important role in insulin resistance, it does not mean that diet and exercise are not important. In fact, it is likely the interplay between an unhealthy diet and an unfortunate microbiome composition that is at play here,” concludes Henrik Bjørn Nielsen.