Chronic High‐Salt Intake Reprograms Metabolic Homeostasis Driven by Dietary Rice Varieties via Microbial and Metabolite Associations

ABSTRACT

The top two dietary mortality risk factors globally are low whole grain consumption and excessive salt intake, posing particularly acute challenges in Asia. Given the dual burden of excessive salt and refined carbohydrate intake in rice‐dependent populations, this study employed 2% salt in combination with white, unpolished, or black rice for 10 months. This model simulated the long‐term impacts of chronic high‐salt intake and refined carbohydrate intake in real life on glucose homeostasis, inflammation, gut microbiota composition, and the serum metabolome. By assessing blood glucose indicators and integrating multi‐omics approaches, the diet‐microbiome‐metabolite interactions were investigated. Black rice (BR) demonstrated context‐dependent effects. In the non‐salt groups, BR improved glucose tolerance and enhanced short‐chain fatty acids (SCFAs) via enrichment of Lactobacillus . However, high NaCl abolished these benefits, which were accompanied by Lactobacillus depletion and Enterobacter enrichment. Salt distinctly remodeled microbial functionality across the different rice varieties. Notably, salt increased blood pressure and OGTT‐AUC only in the black‐rice background, and increased GHbA1c in the unpolished‐rice background, whereas total SCFAs differed by rice type rather than by salt. Our findings established that the influence of salt was inseparable from staple food matrices, underscoring the necessity for context‐specific dietary guidelines.