HUMAN STOOL METABOLOMES DIFFER UPON 24-HOUR BLOOD PRESSURE LEVELS AND THE NON-DIPPING BLOOD PRESSURE PROFILE

Abstract

Objective: Dysbiosis of gut microbiota (GM) has been implicated in the pathophysiology of arterial hypertension (HT), via a putative role of food-derived short chain fatty acids (SCFAs) and other metabolites. Among the clinical manifestations of HT, the absence of a significant drop in blood pressure (BP) overnight (i.e. the non-dipping BP profile) has been associated with poor cardiovascular outcomes. The link between GM and the non-dipping BP profile is unknown. Design and method: After informed consent, 16 male patients (mean age = 52.3 ± 12.4 years; 1 patient under beta blocker) and their female partners (n = 10; mean age = 46.5 ± 13.2 years; 1 patient under thiazide diuretic and angiotensin-converting-enzyme inhibitor) were subjected to 24-hour ambulatory BP monitoring and categorized in 2 groups: HT (n = 6 men and 1 woman) and normotension (n = 19). According to the conventional night/day BP ratio >0.9, 15 individuals (n = 8 men and 7 women) were categorized as non-dippers. Metabolomics using Nuclear Magnetic Resonance was performed on stool samples, including the quantification of the 3 main SCFAs (i.e. acetate, propionate and butyrate). Results: Principal component analyses (PCA) discriminated HT versus normotensive individuals on the basis of the stool metabolomes of the entire cohort (Q2 = 0.10). PCA also discriminated dippers versus non-dippers upon the stool metabolomes of the male and female cohorts (Q2 = 0.76 and 0.98, respectively) or the entire cohort (Q2 = 0.27). Significant correlations between stool metabolomes and the mean 24-hour BP levels were highlighted in male and female cohorts (R2 = 0.63 and 0.79, respectively), as well as in the entire cohort (R2 = 0.54). Interestingly enough, a higher variation between stool metabolomes (represented by the measure of inertia) was found in couples with a different BP status (51.4% of inertia) compared to the couples in whom both individuals presented with the same BP status (37.5% of inertia). The propionate/butyrate ratio was higher in the stools of male HT patients versus male normotensive patients (p = 0.03), but no difference was observed in the female cohort or in the entire cohort. Conclusions: In conclusion, this 26-patient cohort highlights significant correlations between the stool metabolome and (i) BP levels and (ii) the non-dipping BP profile in both genders.