Chrono‐Synergistic Nutrition: Gut Microbiota–Targeted Diets and Circadian‐Aligned First Meal Timing Confer Robust Protection Against Kidney Stone Formation

The emerging gut-kidney axis paradigm suggests that dietary modulation of gut microbiota may influence nephrolithiasis pathogenesis, while the specific dietary components and the temporal dimension of nutritional intake remain unexplored. This study introduces a novel framework integrating gut microbiota-targeted dietary quality with circadian-aligned meal timing to elucidate their synergistic role in kidney stone prevention. We conducted a comprehensive analysis of 21,840 adults from the NHANES cohort (2007-2016), investigating the independent and combined associations of the Dietary Index for Gut Microbiota (DI-GM) and First Meal Timing (FMT) with kidney stone prevalence. Multivariable logistic regression models and restricted cubic spline analyses elucidated dose-response relationships, while stratified analyses explored population heterogeneity. Our investigation unveiled a compelling narrative of dietary protection: elevated DI-GM scores conferred significant nephroprotection, with the most pronounced benefits observed in participants consuming microbiota-supportive diets. Early meal initiation during the breakfast window (00:00-09:00) independently reduced stone risk compared to delayed feeding patterns. Remarkably, the convergence of optimal dietary quality with circadian-aligned meal timing created a synergistic protective shield, yielding the most substantial risk reduction and suggesting that temporal nutrition strategies may amplify the benefits of gut microbiome modulation. This pioneering investigation establishes the foundational evidence for precision chrono-nutritional interventions in kidney stone prevention. By harmonizing microbiome-targeted dietary optimization with circadian meal timing, our findings illuminate a transformative pathway toward personalized therapeutic strategies that transcend conventional nutritional paradigms, offering new hope for millions affected by recurrent nephrolithiasis.