How an unhealthy gut promotes cardiovascular disease.

Associate Professor Shane Thomas, University of New South Wales

Vanguard Grant

Years funded: 2026 - 2028

Atherosclerotic cardiovascular disease (ACVD) is a chronic inflammatory condition resulting in the formation of atherosclerotic plaques within the walls of arteries, which impede blood flow through the artery. Atherosclerotic plaques can rupture and block artery blood flow to cause a heart attack, a leading cause of death in Australia and worldwide. This project examines how an unhealthy gut microbiome promotes ACVD, which can offer new ways to diagnose and treat ACVD. The gut microbiome is a large complex community of microorganisms living in the large intestine that plays important roles in food digestion and metabolism and maintains human health. However, an unhealthy gut microbiome is linked to the development of serious diseases including ACVD. In ACVD patients, the composition and function of the gut microbial community is significantly changed, resulting in the leakage of microbes into blood and increased production of dangerous metabolites that promote ACVD. However, how the gut microbiome changes to cause ACVD is poorly understood. Using an advanced artificial intelligence-assisted computational approach to comprehensively analyse complex datasets of gut microbial genes (called metagenomics) we have compared the microbiomes in healthy individuals and ACVD patients and identified unique signature changes in the composition of gut microbial species in human ACVD patients. In this project, we will now perform a more in-depth computational analysis of shotgun metagenomics datasets from a larger world-wide population of healthy individuals and ACVD patients (>18000 individuals) to provide a comprehensive understanding of how microbiome composition and function is altered during ACVD. The computational analyses will be complemented by studies in a new ‘humanised microbiome’ mouse model of ACVD, where the gut microbiomes from ACVD patients or healthy individuals will be transplanted into experimental mice to (i) understand how the altered microbiomes from human ACVD patients cause disease, and (ii) identify specific bacterial strains responsible for modulating ACVD. By combining the computational analysis of large human metagenomic datasets with studies in a new ‘humanised microbiome’ mouse model of ACVD, this project will provide comprehensive new information on how the gut microbiome changes in human ACVD to cause disease. This new information will (i) identify a set of gut microbiome signature changes for developing a new stool-based clinical test for determining ACVD patient's gut health and their risk of heart attack, and (ii) allow the formulation of new personalised probiotic therapeutics that restore ACVD patient's gut microbiome health and reduce their risk of heart attack.