Integrative analysis of gut-brain axis-related comorbidity between ulcerative colitis and Parkinson’s disease and screening of candidate bioactive compounds from 44 medicinal and edible fruits

Background To explore the potential genetic associations and comorbidity mechanisms between Ulcerative colitis (UC) and Parkinson’s disease (PD), and to screen a library of 44 dual-use fruit sources for potential bioactive compounds. Methods Mendelian randomization and transcriptome analysis were employed to investigate the shared mechanisms between UC and PD. A PD diagnostic model was constructed based on intersecting genes, and interpretability analysis was conducted using the Shapley Additive Explanations algorithm. Model performance was evaluated using both an internal validation cohort and an independent external GEO cohort. Further integration of network pharmacology, molecular docking, and molecular dynamics simulations was employed to screen for active components in the 44 dual-use fruit sources, analysing their potential targets and associated mechanisms. Results Mendelian randomization analysis suggested a potential genetic association between UC and PD. Transcriptome analysis revealed that shared molecular features were primarily enriched in inflammation- and immune-related pathways. A PD diagnostic model constructed using 20 intersecting genes demonstrated good discriminatory ability. The results of network pharmacology and molecular simulations further suggested that multiple active components from the 44 food-medicine dual-use fruit-derived compounds exhibit multitarget effects on inflammation, oxidative stress, and neuroprotection. These components may modulate the UC-PD comorbidity process through gut-brain axis-related pathways. Conclusion From an integrative computational analysis perspective, this study suggests potential links between UC and PD across genetic background, inflammatory immune responses, and gut-brain axis mechanisms. It identifies several candidate genes and fruit-derived bioactive compounds warranting further investigation. These findings are intended to propose mechanistic hypotheses and candidate intervention strategies. Further validation is required through in vitro experiments and in vivo studies. Clinical trial number Not applicable.