Exploring the Role of the Gut-Kidney Axis in Determining Salt Sensitivity Phenotypes Among Normotensive Individuals: A Cross-Sectional Study

Abstract

Background: Salt sensitivity of blood pressure varies markedly among individuals, even in normotensive populations, and is increasingly linked to gut microbial composition and function. Emerging evidence supports the gut–kidney axis as a critical regulator of sodium handling, inflammation, and vascular tone. However, data in normotensive individuals remain limited. Objective: To identify whether specific gut microbiome profiles predict blood pressure responses to high dietary sodium intake among normotensive adults. Methods: A cross-sectional study was conducted at a tertiary care hospital in Islamabad over eight months. Ninety normotensive participants (aged 20–50 years) were enrolled and subjected to a controlled low-sodium diet (3 g/day NaCl) for seven days followed by a high-sodium diet (18 g/day NaCl) for another seven days. Blood pressure was monitored daily, and salt sensitivity was defined as a ≥10 mmHg increase in mean arterial pressure (MAP) after the sodium challenge. Stool samples were analyzed using 16S rRNA sequencing (Illumina MiSeq) to assess microbial diversity and composition. Statistical analyses included t-tests, Pearson correlations, and multivariate linear regression, with p<0.05 considered significant. Results: Salt-sensitive individuals (n=45) exhibited significantly greater increases in systolic, diastolic, and mean arterial pressure (ΔMAP = 9.1 ± 3.2 mmHg) compared to salt-resistant participants (ΔMAP = 1.8 ± 1.4 mmHg; p<0.001). Microbiome diversity indices were lower in the salt-sensitive group (Shannon Index: 3.25 vs. 3.79; p=0.012). Lactobacillus spp. showed a negative correlation with ΔMAP (r = –0.48, p<0.001), while Bacteroides fragilis and Ruminococcus gnavus were positively associated with salt-induced blood pressure elevations. Conclusion: Distinct gut microbial signatures are associated with salt sensitivity in normotensive adults. These findings support the predictive potential of the gut–kidney axis and microbiome profiling in identifying individuals at risk for salt-induced blood pressure elevation.