High-sodium and low-potassium (HNaLK) content in Western diets increases the risks of cardiovascular disease and metabolic syndrome. We investigated if the dietary minerals interact with gut bacteria to modulate circulating lipids and/or biogenic amines, which are implicated in cardiovascular and metabolic diseases. Using metabolomic approaches, the effects of gut bacteria depletion (via antibiotic treatment) and HNaLK intake on circulating levels of lipids and biogenic amines were examined in rats. Significant interactions were observed between antibiotic treatment and the HNaLK diet in altering circulating lipids, mainly triglycerides (TGs). Two distinct TG groups differentially regulated by antibiotic treatment were identified. One group (cluster 1), representing the majority of TG species detected, was downregulated, whereas the other group (cluster 2) was upregulated by antibiotic treatment. Interestingly, cluster 2 TGs were also regulated (i.e., downregulated) by the HNaLK diet. Cluster 2 TGs exhibited greater carbon-chain length and double-bond content and included TGs composed of very-long-chain polyunsaturated fatty acids, previously shown to be associated with reduced diabetes risk. We also found a number of plasma biogenic amines altered both by gut bacteria depletion and HNaLK intake, suggesting possible interactions of the diet and gut bacteria in the modulation of these metabolites. The diet effects were observed with significant changes in specific gut bacterial taxa. In conclusion, the HNaLK diet interacts with gut bacteria to alter circulating levels of lipids and biogenic amines, which may be related to its health effects.

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