Sulfur microbial diet and ischemic stroke risk

This study aimed to evaluate the association of dietary pattern linked to sulfur-metabolizing gut microbiota (SMD) with incident ischemic stroke, its dose-response relationship, and population heterogeneity.

This study included 208,415 participants. The SMD score was constructed based on repeated 24-h dietary recall questionnaires (Oxford WebQ) and categorized into quartiles. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline analyses were performed to assess the dose-response relationship. Subgroup analyses, sensitivity analyses, and food substitution analyses were further conducted.

During a mean follow-up of 11.45 years, a total of 3,273 incident ischemic stroke cases were identified. After full multivariable adjustment, compared with participants in the lowest quartile (Q1), those in the highest quartile (Q4) had a 13% higher hazard of ischemic stroke (HR = 1.13, 95% CI: 1.02, 1.25, p = 0.019). Each 1-standard deviation increase in the SMD score was associated with a 4% higher hazard of ischemic stroke (HR = 1.04, 95% CI: 1.01, 1.08, p = 0.018), with a significant linear trend (P for trend = 0.013). Restricted cubic spline analysis suggested an approximately linear association (P for nonlinearity = 0.232). Subgroup analyses showed heterogeneity by ethnicity (P for interaction = 0.003), whereas interactions by age and sex were not statistically significant. Sensitivity analyses yielded generally consistent estimates. Substitution analysis indicated an HR below 1 when low-calorie beverages were replaced with an equivalent energy intake of other vegetables (HR = 0.90, 95% CI: 0.81, 1.01, p = 0.063).

Higher adherence to the SMD was associated with a higher hazard of ischemic stroke in this large prospective cohort, with an approximately linear dose-response relationship. The association was modest and showed some sensitivity to exposure measurement precision, indicating that replication in independent cohorts is warranted.