Stroke remains a leading cause of death and disability. Converging evidence implicates the gut-brain axis via inflammation, metabolic signalling, blood pressure control, thrombosis and intestinal barrier function, in stroke risk and recovery, but robust population scale evidence is lacking. We will quantify how gut related exposures shape incidence, subtype and outcomes of stroke.
Research questions:
1) Which gut linked exposures predict incident ischemic and hemorrhagic stroke?
Metrics: dietary quality/fiber, alcohol, smoking, physical activity, sleep, antibiotics/PPIs/metformin/laxatives, GI disorders such as IBS/IBD/coeliac, obesity/diabetes, oral health, environmental factors including air pollution and deprivation.
2) Among stroke survivors, which exposures predict early and long term outcomes and disability?
Metrics: mortality, recurrence, cognition, depression, disability
3) What biological pathways mediate these associations?
Metrics: lipids, glycaemia and inflammation; proteomic/metabolomic signatures where available
4) Are effects causal and heterogeneous by age, sex, ancestry and deprivation?
Objectives: assemble incident stroke cohorts with matched controls; derive a composite gut-brain exposure (GBx) score; model associations using time updated Cox/Fine-Gray and mixed models with DAG informed adjustment, negative control analyses and sensitivity to misclassification/immortal time bias; perform genetic triangulation (polygenic risk scores and Mendelian randomisation) to probe causality, in imaging subsets, relate exposures to white matter hyper-intensities, micro-structural injury and small vessel disease; develop internally validated prediction tools to prioritise modifiable, gut targeted interventions for prevention and post stroke recovery.