Identification of novel early biomarkers of cardiovascular disease risk and their relationships with bioactive dietary compounds: metabolomic and gut metagenomic approaches

Identifier:  TDX:3837

Handle: https://hdl.handle.net/20.500.11797/TDX3837

Authors:  Calderón Pérez, Lorena

Abstract:
Several risk factors contribute to cardiovascular diseases (CVDs) burden worldwide. Causal and modifiable CVD risk factors, such as hypertension and hypercholesterolemia, have led to the development of risk prediction models and to major developments in therapy. However, not all traditional risk factors are enough to identify all at-risk individuals. The identification of novel CVD risk biomarkers based on metabolome and gut microbiome represent exciting gaps in the early detection of CVDs. The aim of this thesis is to identify novel early gut microbiota- and metabolite-based CVD risk biomarkers suitable for the preliminary stages of human hypertension, hypercholesterolemia and other major CVD risk factors through the integration of multiomics approaches, and to assess their relationships with bioactive dietary compounds to speculate about the involved pathways. An observational approach was used. In a cross-sectional study involving nontreated grade 1 hypertensive and normotensive subjects, by application of metabolomics and gut metagenomics, novel gut microbiota- and metabolite-based biomarkers, including a set of bacterial taxa from Bacteroides spp. and faecal short-chain fatty acids, were strongly associated with hypertension. Moreover, dietary phenolic compounds shown positive and negative relationships with hypertensive-enriched biomarkers, suggesting a complex pathway by which they could be involved in the pathogenesis/prevention of hypertension. In a second cross-sectional study in healthy and moderate-to-high hypercholesterolemic subjects, by application of lipidomics, specific serum lysophospholipids were identified as suitable susceptibility/risk biomarkers against the onset of hypercholesterolemia. These findings were verified in an in vivo study in hamsters. In addition, a positive relationship was found between lysophospholipid biomarkers and dietary omega-(n) polyunsaturated fatty acids, and these results were further investigated in a last systematic review and meta-analysis of randomized clinical trials. With the main biomarkers identified in this thesis a reliable health and disease classifier to discern main CVD risk factors from the healthy status is proposed.