Abstract 18: Excess Dietary Salt-induced Blood Pressure Elevation Is Associated With Impaired Bile Acid Signaling And Human Monocyte Activation

Abstract

Excess dietary sodium (Na + ) is a major risk for hypertension and cardiovascular disease. We previously found that excess dietary salt induces gut microbial dysbiosis and leads to activation of antigen presenting cells and hypertension, but the mechanisms are not known. The gut microbiome metabolizes bile acids, and these have been implicated in activation of antigen presenting cells. We hypothesized that high dietary Na + -induced inflammation leading to hypertension is associated with impaired bile acids signaling. We measured plasma bile acids via a metabolomics analysis in 75 volunteers. Blood pressure was also monitored. Based on the recommendations by the American Heart Association, we classified daily Na + intake <2.3g as normal salt (NS, n=23), and high salt (HS, n=52) for subjects consuming ≥ 2.3g Na + . Spearman correlation was used to assess the relationship between Na + intake and blood pressure. We found that elevated diastolic (r=0.331, p=0.003), systolic (r=0.383, p<0.001) and mean arterial pressure (r=0.278, p=0.014) were associated with increased Na + intake. Five taurine and glycine-conjugated secondary bile acids including taurodeoxycholate (1.320 ± 0.238 vs. 2.820 ± 0.669; p=0.010); glycodeoxycholate (1.197± 0.154 vs. 1.998± 0.432; p= 0.033); glycodeoxycholate sulfate (1.037± 0.132 vs. 1.521± 0.192; p= 0.044); glycolithocholate (0.829± 0.094 vs. 1.622± 0.363; p= 0.006) and glycolithocholate sulfate (1.083± 0.127 vs. 1.598± 0.205; p= 0.030) were lower in the HS when compared to the NS group. Interestingly, using RNA sequencing in human monocytes, we found that the NR1H4 gene which encodes the farnesoid X receptor, a nuclear receptor activated by bile acids, was significantly downregulated by high salt treatment, and this was associated with a pro-inflammatory phenotype (9.80± 1.65 vs. 11.82± 1.64; adjusted p-value=0.043). Our findings suggest that high salt impairs bile acids signaling leading to inflammation and salt-induced hypertension.