Abstract TU191: Urinary sodium and potassium excretions, gut microbiome, circulating metabolites, and cardiometabolic risk

Background: A high-sodium, low-potassium diet promotes hypertension and cardiovascular disease (CVD). Intricate interactions between the gut microbiota and minerals, encompassing absorption, transformation, and signaling, point to an underexplored role of gut bacteria in this diet-cardiometabolic disease association. Aim: To characterize microbial features in response to sodium and potassium, map related shifts in circulating metabolites, and evaluate associations between the identified metabolites and incident cardiometabolic events. Design: In 264 men from the Men's Lifestyle Validation Study, we examined the gut taxonomic and functional compositions in response to 24-hour urinary sodium and potassium excretion. We further assessed plasma metabolomic profiles responsive to the identified gut microbial features and their associations with coronary heart disease (CHD), CVD, and type 2 diabetes (T2D) among 12,225 participants from Nurses' Health Study (NHS), NHSII, and the Health Professionals Follow-up Study. Results: We identified 25 sodium-responsive species, including Collinsella , Desulfovibrio , and Roseburia species, along with 4 potassium- and 4 sodium-to-potassium ratio-responsive species. Microbial scores correlated strongly with urinary sodium, potassium, and their ratio (Pearson r = 0.37–0.57). High-sodium and low-potassium microbiome scores were linked to a favorable plasma metabolomic profile, characterized by higher imidazole propionate, and lower hippuric acid and 3-indolepropionic acid levels. These metabolomic alterations were associated with an increased risk of developing CHD (Quintile5 vs. Quintile1: HR=2.14 [95%CI: 1.53, 2.99]; p-trend < 0.0001), CVD (HR=1.56 [1.34, 1.83]; p-trend < 0.0001), and T2D (HR=3.03 [2.56, 3.60]; p-trend < 0.0001). Conclusions: Our findings linked high sodium and low potassium intake to a specific gut microbial pattern that predicted an adverse metabolomic profile precipitating an elevated risk of developing cardiometabolic conditions. Overall, these data suggest that the human gut microbiome can actively participate in the etiological processes linking high salt intake with adverse health outcomes.