Human diseases, such as skin malignancies, immune-mediated diseases (dermatitis, eczema, inflammatory bowel disease, etc.), metabolic and cardiovascular diseases (diabetes, gout, non-alcoholic fatty liver disease, coronary heart disease, etc.), neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, etc.), and mood disorders, affect the lives of hundreds of millions of people worldwide. Although these diseases are clinically distributed across different organ systems, mounting evidence suggests that chronic immune system dysregulation and metabolic abnormalities may be the common biological thread connecting them. However, this hypothesis has not yet been systematically validated in large population cohorts.
By analyzing the vast and diverse datasets of the UK Biobank, including genetics, proteomics, metabolomics, radiomics, and a wealth of clinical and lifestyle information, we will gain a deeper understanding of the complex biological mechanisms underlying these diseases. We will specifically investigate whether chronic, low-grade inflammation and its associated metabolic alterations (e.g., in insulin signaling, purine metabolism, and gut microbiome-derived metabolites) constitute the “soil” for the coexistence of these seemingly disparate diseases. By simultaneously studying multi-layered biological information, we can identify common molecular patterns and discover specific biomarkers that can predict susceptibility and progression of this disease spectrum. The project is expected to last 36 months.
The knowledge generated by this project will contribute to understanding the common etiologies of these diseases and pave the way for the development of personalized and targeted interventions against core immune-metabolic dysfunctions, ultimately improving patient care and reducing the burden of chronic diseases.