Chronic high-salt diet induces cognitive impairment and anxiety through gut microbiota alterations

A high-salt diet (HSD) induces cognitive impairment and anxiety, with gut microbiota alterations serving as a potential underlying mechanism. Six-month-old male C57BL/6J mice were randomly assigned to the high-salt diet group (HS, n = 10, 8% NaCl) and the control group (ND, n = 10, 0.4% NaCl), and maintained on their respective diets for 180 days. Behavioral tests were conducted to assess the impact of chronic HSD on cognition and anxiety-like behaviors in mice. Hippocampal neuroinflammation was evaluated by RT-qPCR analysis, while neuronal damage was quantified using Nissl and NeuN staining. Correlation analysis was conducted to explore associations between differential gut microbiota and differentially expressed genes (DEGs) in the hippocampus. Our results demonstrated that HSD impaired cognition and emotion in mice through gut microbiota changes and hippocampal gene alterations, which subsequently promoted neuroinflammation and neuronal damage. Our study revealed that HSD increased Dubosiella and Anaeroplasma while decreasing Prevotellaceae_UCG_001 in the gut microbiota, upregulated Btbd16, Il1b, Prlr, Cd24a, Ak7, while downregulating Casp4 in hippocampal gene expression. Correlation analysis revealed significant correlations between Dubosiella and Il1b/Cd24a, Anaeroplasma and Ak7/Prlr/Casp4, Prevotellaceae_UCG_001 and Btbd16/Ak7. In summary, chronic HSD triggers gut microbiota dysbiosis and hippocampal gene expression changes, ultimately driving neuroinflammation and neuronal damage in the hippocampus, which culminates in cognitive deficits and anxiety. These findings provide new insights into the potential mechanisms of HSD-induced cognitive impairment.