Genetics, epigenetics and environmental factors, dietary salt being the largest one, contributing to the development of salt-sensitive hypertension is well known and intensely researched. Added to these factors, new evidence from our laboratory and others indicates that gut microbiota constitute an important additional factor influencing the extent of blood pressure of an individual. The host genome being `rigid', whereas the microbiome being relatively flexible (because it is relatively easier to alter compositions of gut microbiota) makes it an attractive proposition to contemplate microbiota-driven strategies for the clinical management of hypertension. However, fundamental questions on how the genome, epigenome or dietary salt modify microbiota remain to be determined. To address this point, the current proposal takes advantage of preliminary data generated with studies on the genome and epigenome of the most popular salt-sensitive hypertensive rat model, the Dahl Salt- sensitive (S) rat and, proposes to study how the host genetic and epigenetic factors interact with both gut and oral microbiota to facilitate salt-sensitive BP regulation. To our knowledge, this will be the first methodical investigation into the host genome-microbiome interactions in salt-sensitive hypertension. Our work will be expected to provide fundamental insights into important, yet undiscovered new mechanisms governing the genesis of hypertension involving the microbiota as a new player.
Aided by preliminary data, the current proposal seeks to address the fundamental relationship between gut and oral microbiota and the host in the context of salt-sensitive hypertension. Genetic and epigenetic cause-effect relationships will be examined using an integrated approach of using custom genetically-altered rat strains and metagenomic, metatranscriptomic and metabolomics approaches.