Bidirectional gut-heart axis interactions in the context of predictive, preventive, and personalised medicine: A time-course analysis of comorbidity and mortality risk in a large population cohort
Author Identifier (ORCID)
Youxin Wang: https://orcid.org/0000-0002-6574-6706
Abstract
Background: Gastrointestinal (GID) and cardiovascular diseases (CVD) often coexist, making integrated predictive, preventive, and personalised medicine (PPPM/3PM) management challenging. Although GIDs are established CVD risk factors, their bidirectional link remains unclear, hindering early risk stratification and tailored interventions. Methods: This bidirectional study enrolled 460,899/405,701 participants without baseline CVD/GID from the UK Biobank cohort. Associations of GID/CVD with CVD/GID incidence, and associations of comorbidities with all-cause mortality among GID/CVD patients, were estimated via time-dependent Cox regression models. Results: During a median follow-up of 13.5/13.2 years, 70,435 CVD cases and 113,191 incident GID cases occurred. Patients with GID had an elevated risk of CVD (adjusted hazard ratio [aHR] = 1.33, 95% confidence interval [CI] = 1.31–1.35); conversely, patients with CVD had an increased risk of GID (aHR = 1.41, 95% CI = 1.39–1.44). As the number of exposures increase, the risk of outcomes increased progressively. Highest risk occurred within the first year following exposures, with a gradual decline over time. The associations with mortality were identified in CVD diagnosed after GID (aHR = 3.63, 95% CI = 3.51–3.76) and GID diagnosed after CVD (aHR = 1.86, 95% CI = 1.79–1.94). Conclusions: We identified a bidirectional GID–CVD link, with each increasing the other’s risk by 33–41%. Risk peaks within the first year post-diagnosis—defining a critical window for early intervention—and increases with cumulative disease burden. Comorbidity markedly increased mortality (3.6-fold for CVD after GID; 1.9-fold for GID after CVD). These findings highlight the value of integrating GID and CVD monitoring into PPPM strategies for early prediction, targeted prevention, and personalised management to reduce comorbidity and mortality.
Keywords
Cardiovascular disease, coexistence, gastrointestinal disorder, gut‒heart axis-related disorders, improved individual outcomes, risk stratification, survival, PPPM/3PM strategies
Document Type
Journal Article
Date of Publication
1-1-2026
Publication Title
EPMA Journal
Publisher
Springer
School
School of Medical and Health Sciences
Funders
This work was supported by the Yanzhao Gold Talent Project of Hebei Province (HJZD202506), the National Natural Science Foundation of China (82473717), and the Beijing Municipal Health System Special Funds of High-Level Medical Personnel Construction (grant no. discipline backbone-03-47). The funders had no role in the study design, data analysis, interpretation of the data, or preparation of the manuscript.
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Comments
Cao, M., Liu, D., Wang, H., Li, C., Lin, H., Wu, L., & Wang, Y. (2026). Bidirectional gut-heart axis interactions in the context of predictive, preventive, and personalised medicine: A time-course analysis of comorbidity and mortality risk in a large population cohort. EPMA Journal. Advance online publication. https://doi.org/10.1007/s13167-026-00449-4