Mediating role of the Dietary Index for Gut Microbiota in the association between depression and cardiovascular health among US adults
Dose-response
Abstract
Background Depression is closely associated with cardiovascular health, and gut microbiota–related dietary patterns may represent a potential biological pathway linking the two. This study aimed to examine the association between depressive symptoms and cardiovascular health as defined by Life’s Essential 8 (LE8), and to evaluate the mediating role of the Dietary Index for Gut Microbiota (DI-GM) in this association. Methods The study included 18,071 adults aged ≥ 20 years from the US National Health and Nutrition Examination Survey (NHANES) 2007–2018. The primary outcome was LE8 cardiovascular health rating (low/moderate/high), with LE8 continuous total score as supportive outcome; depression was assessed by Patient Health Questionnaire (PHQ-9). Survey-weighted ordinal logistic regression and linear regression were used to assess the association between depression and DI-GM and LE8. Restricted cubic spline (RCS) was used to evaluate the dose-response relationship, and counterfactual (g-computation) mediation analysis was used to explore the mediating effect of DI-GM. Effect modification was also examined in subgroups. Models were adjusted for age, sex, race/ethnicity, marital status, education level, and poverty-to-income ratio (PIR). Results After adjusting for potential confounders, each 1-point increase in PHQ-9 was associated with a 9% reduction in the cumulative odds of having a higher LE8 score (OR = 0.91, 95% CI: 0.90–0.93), whereas each 1-point increase in DI-GM was associated with a 46% increase in the cumulative odds of having a higher LE8 score (OR = 1.46, 95% CI: 1.42–1.51) (both P < 0.001). DI-GM partially mediated the association between depression and LE8, the total natural indirect effect was statistically significant (TNIE OR = 0.996, 95% CI 0.993–0.999, P = 0.008), accounting for 5.08% (95% CI 1.35–8.87%) of the total association, estimated within a counterfactual mediation framework. This mediating pathway was more pronounced among women (mediation proportion: 6.0%) and individuals with comorbid gastrointestinal diseases (14.2%). Dose–response analyses indicated that these associations generally followed a monotonic pattern. Conclusions A greater burden of depressive symptoms was associated with poorer cardiovascular health as assessed by LE8, suggesting that gut microbiota-related dietary patterns may partially mediate the association between depression and cardiovascular health. DI-GM may represent a potential modifiable target, particularly among women and individuals with comorbid gastrointestinal diseases. However, the temporal sequence and underlying mechanisms of these associations require further validation through longitudinal and intervention studies.
- Gut microbiota-related dietary patterns
- Dietary Index for Gut Microbiota
- Depression
- Depressive symptoms
- Life's Essential 8
- Humans
The paper
Huazhong University of Science and Technology
Research Square, 16 Oct 2026, Open access, Preprint, not peer-reviewed


