Probiotic Intake May Protect from All-Cause Mortality and Especially Cardiovascular Mortality in People Without Diabetes

Introduction: This study examined the association between probiotic/prebiotic intake and all-cause and cause-specific mortality among American adults stratified by glycemic status. Methods: We included participants with probiotic/prebiotic intake and follow-up data from NHANES 1999-2016. Mortality was linked to the National Death Index. Cox proportional hazards models with three levels of covariate adjustment were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Stratified analyses assessed result stability. Results: Among 13,604 adults (6,886 non-diabetic, 4,210 prediabetic, 2,508 diabetic), probiotic intake in the non-diabetic group was associated with reduced all-cause mortality (HR (95% CI) 0.68 (0.52, 0.88), P = 0.003) and cardiovascular disease (CVD) mortality (HR (95% CI) 0.43 (0.25, 0.71), P < 0.001). Yogurt consumption alone was similarly associated with lower all-cause (HR (95% CI) 0.70 (0.54, 0.90), P = 0.005) and CVD mortality (HR (95% CI) 0.45 (0.26, 0.78), P = 0.005). No significant associations were found in prediabetic or diabetic groups. Discussion: The protective association was observed only in non-diabetic individuals and may be partially mediated by socioeconomic and clinical factors. The lack of association in dysglycemic groups may be attributed to advanced metabolic dysregulation, concomitant medications, and gut microbiota alterations. Residual confounding cannot be excluded. Conclusion: Probiotic intake is associated with lower all-cause and CVD mortality in nondiabetic adults, but not in those with prediabetes or diabetes. These findings suggest population- specific effects and highlight the need for further clinical trials to establish causality.