Reasearch Projects

The current main research interests of Orho-Melanders´research group are related to prediction and prevention of cardiometabolic diseases with main focus in genetic and circulating biomarkers, diet, gut microbiota and causal risk factors in population based cohorts.

The role of gut microbiome in cardiometabolic diseases: with focus on diet, bacteriophages and causal inferences in two large longitudinal Malmö cohorts

BACKGROUND: Despite evidence supporting a role for the gut bacteria in multitude of human diseases including type 2 diabetes (T2D) and cardiovascular disease (CVD), causal- and mechanistic evidence in humans is limited, and prospective studies are lacking. The gut bacterial composition can be modified by environmental factors as probiotics and dietary changes, and by gut bacterial viruses, bacteriophages/prophages (phages). Therefore, it is important to understand how dietary factors and phages regulate the gut bacterial equilibrium, and connect to cardiometabolic risk.

OBJECTIVES: We challenge the question of interrelationships between bacteria and phages in human fecal samples and investigate their connection to dietary intakes and the future risk of T2D and CVD. For this purpose, we will integrate clinical phenotype data with multi-omics data of human (genomic, metabolomic, proteomic) and gut origin to clarify connections between dietary patterns/intakes, host genetic factors, circulating metabolites and inflammatory proteins and gut microbiota composition, diversity and functional capacity, and how such connections relate to risk of cardiometabolic disease (CMD).

WORKPLAN: In two large population cohorts, the SCAPIS-Malmö (N=5008) and Malmö Offspring Study (N=3700), we investigate how gut microbiota composition, diversity and functional capacity are related to diet and associate with cardiometabolic risk traits and incidence of T2D and CVD. We perform novel type of shotgun metagenomic analysis with precision and coverage far beyond the classical reference -based approaches, enabling detection and quantification of all bacterial species to strain level, and phages. By Mendelian Randomization we study causal connections and directions between gut microbiota, metabolites and risk of T2D and CVD. By Machine Learning we elucidate hidden connections and hierarchies in the multi-omic data in relation to CMD.

SIGNIFICANCE: Our study will determine interrelationships between gut bacteria and phages and provide prospective evidence for the role of the gut bacteria and their virus in CMD. Further, we expect to identify individual bacterial species/strains and phages that via dietary patterns relate to risk of CMD. Our study will identify risk groups for future interventions, and has the capacity to detect potential new probiotic bacterial strains and to evaluate the potential of phage in future diagnostic and therapeutic applications.

GRANT SUPPORT: Our studies are supported by the European Research Council (consolidator grant 649021) the Swedish Research Council, the Region Skåne University Hospital), the Swedish Heart and Lung Foundation, the European Foundation for Study of Diabetes (EFSD 2015/338), the Novo Nordic Foundation, the Albert Påhlsson Foundation and the Swedish Diabetes Foundation.