A kick in the guts Insulin resistance, gut microbiota and cardiometabolic diseases

In this thesis we show that bacteria in the gut are associated to many aspects of metabolism in prediabetes, diabetes and cardiovascular diseases. We identified changes in metabolism associated to insulin resistance in individuals with the metabolic syndrome, which were previously unknown. In particular certain proteins related to inflammation were strongly associated to insulin resistance. Previous studies have indicated that compounds produced by bacteria in the gut can have beneficial or detrimental effects on health. One metabolite called Imidazole propionate (ImP) from histidine metabolism has been shown to result in insulin resistance when injected to mice. This is of importance, because histidine is abundant in proteins such as nuts and meat and typically individuals with diabetes get recommendations to consume less sugars and simple carbohydrates and more proteins. Therefore, the questions we wanted to answer was: (1) is dietary histidine resulting in higher levels of ImP and (2) is supplementation of histidine detrimental for insulin resistance? We found that histidine supplementation increased ImP levels but that histidine supplementation also improved blood sugar levels, indicating an improvement in insulin resistance. Finally, we show that bacteria in the gut are associated to cardiovascular diseases in a multi ethnic study. We find a trophic network of bacteria to be inversely associated to cardiovascular diseases and triglyceride levels. We hypothesize that gut microbiota might influence cardiovascular diseases by affecting blood lipid levels. However, future studies should confirm our findings in a randomized trial.