Research Question & Objectives
Gastrointestinal diseases-colorectal cancer, IBD, NAFLD, peptic ulcer-are rising public-health burdens. Genetic and environmental drivers are known, yet how environmental exposures, psychosocial stressors, and multi-omic profiles interact remains unclear. Using UK Biobank, we will (1) discover novel biomarkers via integrated omics-environment-psychosocial analyses; (2) clarify causal links among exposures, molecular changes, and disease progression; (3) build machine-learning models for early risk prediction and targeted prevention.
Scientific Rationale
Colorectal cancer is a leading cause of cancer death, shaped by genetics, lifestyle, and metabolism. Radiotherapy for pelvic cancers frequently causes chronic radiation-induced intestinal injury. Despite distinct etiology, it shares inflammation and immune dysregulation with other GI diseases, offering a cross-disease model. Circulating proteins, metabolites, and imaging biomarkers illuminate mechanisms. Chronic stress and depressive symptoms amplify gut inflammation and are amplified by immune-metabolic imbalance. Environmental stressors-air pollution, poor diet, sedentary behavior-modulate the gut-brain axis via microbiota, immunity, and neuroendocrine pathways. Most studies examine single omics or isolated exposures, ignoring bidirectional psychosocial interactions. Integrating genomics, proteomics, metabolomics, high-resolution environmental data, mental-health assessments, and accelerometry-derived physical activity will reveal new pathways, refine risk stratification, and guide precision prevention. Advanced causal-inference and machine-learning tools will ensure robust, predictive models ready for translation.