Venous leg ulcers (VLUs) represent the most severe manifestation of chronic venous disease and are associated with substantial morbidity, healthcare costs, and impaired quality of life. Despite advances in compression therapy and venous intervention, many ulcers are slow to heal or recur, indicating incomplete understanding of underlying biological mechanisms. Emerging evidence suggests that the gut microbiome influences systemic inflammation, immune regulation, endothelial function, and tissue repair, all of which are relevant to venous ulcer pathophysiology. However, the relationship between gut microbial composition and VLU risk has not been systematically investigated at scale.
This project aims to investigate the potential causal relationship between gut microbiome features and the development of VLUs using large-scale human genetic data. Genome-wide association study (GWAS) summary statistics for gut microbiome taxa from the MiBioGen consortium will be integrated with individual-level genetic and phenotypic data from UK Biobank. The primary research questions are: (1) Are genetically predicted differences in gut microbiome composition associated with risk of VLUs? (2) Do specific microbial taxa exert protective or deleterious effects on VLU susceptibility? (3) Are observed associations independent of established cardiometabolic and inflammatory risk factors?
The primary objective is to use Mendelian randomisation and complementary genetic epidemiological approaches to assess causality between gut microbiome traits and VLUs. Secondary objectives include exploring shared genetic architecture and potential biological pathways linking microbial variation to venous disease severity. By leveraging population-scale data, this study seeks to generate novel insights into disease mechanisms and identify potential targets for future preventative or therapeutic strategies.