Diet and gut microbiota in cardiometabolic health: Studies from the Danish Diet, Cancer and Health – Next Generations Cohort and the sub-cohort MAX

Abstract: Cardiometabolic diseases (CMD) are the leading cause of death globally. Diet is a key preventive factor of CMD and a determinant of gut microbiota. Gut microbiota, diet and their interactions have been associated with CMD. In observational studies, diet is measured by self-reported instruments, that need to be validated before use. Gut bacteria vary over time within an individual, making it challenging to study their relationship with health outcomes. Moreover, different dietary patterns may be associated differently with gut microbiota, but few studies exist.    The overall aim of this thesis work was to investigate the role of diet, gut microbiota and their interplay in cardiometabolic health. The MAX sub-cohort from the Diet, Cancer and Health – Next generations (DCH-NG) cohort was established to: validate the DCH-NG food frequency questionnaire (FFQ), validate a dietary quality score (DQS) and associate it with CMD risk factors, investigate gut microbiota temporal variability and associate these with dietary patterns and investigate the direct and indirect effects of a healthy Nordic and Mediterranean diet on CMD risk factors, mediated by gut microbiota.      The FFQ provided satisfactory ranking of individuals according to energy and nutrient intakes. The DQS was useful to rank individuals into groups of having unhealthy, average and healthy dietary habits. Healthy dietary habits were associated with lower levels of several CMD risk factors. Among bacterial genera, 39% had moderate to good reproducibility (ICC>0.5). Gut microbial subgroups (Bacteroides, Prevotella 9 and Ruminococcaceae) were identified and adherence to plant-based dietary patterns differed between subgroups. Healthy Nordic and Mediterranean diets were associated with lower levels of adiposity, but no indirect effect mediated by gut microbiota (Prevotella-to-Bacteroides ratio) was found. However, healthy Nordic and Mediterranean diets were associated with lower levels of lipidemia and hs-CRP, mediated by adiposity.       In conclusion, the DCH-NG FFQ can be used to rank individuals according to dietary intake in epidemiological studies and the DQS is a good indicator of overall diet quality. Different dietary patterns associated differently with gut microbial subgroups and specific genera. There was an effect of diet on CMD risk factors, though this effect was not mediated by the gut microbiota.