Dietary Index for Gut Microbiota and All-Cause Mortality in CKM Syndrome: Evidence of a J-Shaped Association and Partial Mediation by DII and CDAI

INTRODUCTION: Cardiovascular-kidney-metabolic (CKM) syndrome is a multisystem condition involving metabolic abnormalities and organ injury. While diet may influence health outcomes by modulating the gut microbiota, its association with mortality risk in patients with CKM syndrome remains unclear. This study aimed to examine the association between the Dietary Index for Gut Microbiota (DI-GM) and risks of all-cause and cardiovascular disease (CVD) mortality among individuals with CKM syndrome. METHODS: This cohort study included 7,291 adults aged ≥ 20 years with CKM syndrome from NHANES 2009-2018. The DI-GM score (range 0-14; higher scores indicating a more favorable diet for beneficial microbiota) was derived from 14 dietary components and categorized into quartiles. Mortality outcomes were ascertained via linkage to the National Death Index. Multivariable Cox models were used to estimate Hazard Ratios (HRs), and restricted cubic splines examined dose-response relationships. Subgroup and mediation analyses were also conducted. RESULTS: During follow-up, 546 all-cause and 166 CVD deaths were recorded. After adjustment, DI-GM showed a nonlinear association with all-cause mortality. Compared with the lowest quartile (Q1), the third quartile (Q3) had a significantly lower risk, whereas the highest quartile (Q4) showed no significant association. No significant link was observed between DI-GM and CVD mortality. Subgroup analyses indicated stronger protective effects in those with higher education, alcohol consumption, and without chronic kidney disease. Mediation analysis suggested that antioxidant and anti-inflammatory pathways partially explained the association. DISCUSSION: DI-GM shows a J-shaped association with all-cause mortality in CKM syndrome, partially mediated by DII and CDAI, suggesting gut-inflammation pathways. CONCLUSION: Among patients with CKM syndrome, a moderate DI-GM score is associated with lower all-cause mortality risk, potentially mediated through anti-inflammatory and antioxidant mechanisms. DI-GM may help identify high-risk populations and inform dietary interventions.