Associations between dietary index for gut microbiota and stroke, and the mediating role of inflammation: a prospective cohort study

<i>Background</i>: There has been a growing focus on the link between diet, gut microbiota, and stroke. The dietary index for gut microbiota (DI-GM), a novel indicator reflecting the effect of diet on gut microbiota diversity, has not been extensively studied in relation to stroke. This study aimed to examine the association between DI-GM and stroke, and to explore the potential mediating role of inflammatory biomarkers. <i>Methods</i>: We included 124 943 participants from the UK Biobank without stroke at baseline. The DI-GM was calculated using 24-hour dietary assessments. Cox proportional hazard models were employed to analyze the longitudinal associations of DI-GM with stroke and its subtypes. Restricted cubic spline (RCS) and subgroup analyses were also performed. Additionally, mediation analyses were conducted to explore the potential mediating role of inflammatory biomarkers between DI-GM and stroke risk. <i>Results</i>: During a median follow-up of 11.08 years, 3741 participants experienced a stroke, including 1626 ischemic strokes and 536 hemorrhagic strokes. After adjusting for covariates in the main model, higher DI-GM was significantly associated with reduced risks of stroke (HR = 0.97, 95% CI, 0.95-0.99, <i>P</i> < 0.001) and ischemic stroke (HR = 0.96, 95% CI, 0.94-0.99, <i>P</i> = 0.008), but not hemorrhagic stroke. No significant non-linear association was observed in the RCS analysis. Mediation analyses indicated that inflammatory biomarkers, including C-reactive protein, neutrophils, monocytes, leukocytes, neutrophil-to-lymphocyte ratio, and INFLA-score, partially mediated the association, accounting for 2.82% to 10.40% of the total effect. <i>Conclusions</i>: Higher DI-GM was associated with a reduced risk of stroke, particularly ischemic stroke. This protective association may be partially mediated by reductions in serum inflammatory biomarkers.