Abstract Body:
Introduction & Hypothesis: Dahl Salt-Sensitive (SS/MCW) rats on a plant-based wheat gluten diet are significantly protected from salt-induced hypertension, renal damage, and renal inflammation compared to SS rats fed an animal-based casein diet. Here we hypothesized that this protective plant-based diet remodels the gut microbiota and its metabolites.

Methods & Results: From weaning, male SS were fed a 0.4% NaCl AIN-76A diet containing either casein or wheat gluten as the protein source, then challenged at 9 weeks of age to a 4.0% NaCl AIN-76A casein-based, high salt diet for 3 weeks (n=9-10). Based on endpoint fecal 16S gene sequencing, there were significant differences in gut microbiota β-diversity (Weighted Unifrac, p=0.007), and LEfSe analysis demonstrated that Turicibater and Ileibacterium respectively discriminated the gut microbiota of wheat gluten- and casein-fed SS rats. Mass spectrometry-based analyses of metabolites showed that wheat gluten-fed SS rats had significantly lower circulating levels of the detrimental gut-derived metabolites, carnitine (25.2±1.5 vs 33.6±2.0µM), TMA (10.2±0.6 vs 13.7±0.8µM), and TMAO (0.66±0.04 vs 0.91±0.10µM).

To study the translational implications of these findings, we utilized stool and plasma samples acquired from the African American participants of the longitudinal Georgia Cardiovascular Twin Cohort (n=98, 71% females, age 36±4 years) to assess gut microbiota composition and metabolites in humans. Three-day 24-hour dietary recall was obtained through the NIH ASA24 dietary assessment tool, where plant-based dietary index (PDI) was calculated. Higher PDI values indicate higher adherence to a plant-based diet. PDI negatively associated with both SBP (p=0.008) and DBP (p=0.011), and positively associated with gut microbiota α-diversity (Shannon entropy, p<0.001). The majority of the individual TMAO-related metabolites (carnitine, choline, betaine, TMA, and TMAO) tended to positively associate with SBP, with choline reaching significance (p=0.005). Mixtures analysis using the Weighted Quantile Sum (WQS) approach determined that the overall effect of the TMAO panel significantly associated with SBP (beta=5.14, p=0.001), where one unit increase in the WQS index was associated with a 5.14mmHg increase in SBP.

Conclusions: A plant-based diet in both Dahl SS rats and humans appears to have beneficial effects on the gut microbiota and downstream metabolites, potentially contributing to improved blood pressure regulation.