Abstract 059: Deficiency of Either Prebiotic Dietary Fibre or Prebiotic-Responsive Gut Microbiota Result in High Blood Pressure

Background: High fibre intake is associated with lower blood pressure (BP) in epidemiological and clinical studies. Prebiotic fibre resists digestion in the upper gastrointestinal tract and is fermented by gut microbiota in the intestine. The impact of lack of prebiotic dietary fibre in BP remains unknown. Objectives: To determine the consequences of lack of prebiotic dietary fibre to the development of hypertension through changes in the gut microbiome, associated receptors and immune-based mechanisms using a slow pressor angiotensin II (Ang II) model. Methods: C57BL/6 mice were fed a ‘no fibre’ or ‘high fibre’ diets for 3-weeks prior to sham or Ang II minipump implantation (n=4-21/group), and were followed for 4-weeks post-surgery. Gnotobiotic mice received faecal transplant from ‘no fibre’ sham or Ang II mice (n=5-6/group). Cardiac function, BP and gut microbiome (by 16S sequencing) were determined. Results: Ang II mice that received a ‘no fibre’ diet had significantly higher BP than sham (SBP mean±SEM: 143.7±3.5 vs 91.2±1.8, P<0.001) or ‘high fibre’ Ang II mice (143.7±3.5 vs 125.7±5mmHg, P<0.001). Transfer of a hypertensinogenic microbiota to gnotobiotic mice recapitulates the prebiotic-deprived hypertensive phenotype (93.5±3 vs 107±3mmHg, P=0.017). Re-introduction of short-chain fatty acids (SCFAs; produced during fermentation of prebiotic fibre in the large intestine) acetate, propionate and butyrate to fibre-depleted mice had protective effects on the development of hypertension (143.7±3.5 vs 93±1.2, 112.8, 115.2mmHg, respectively), cardiac hypertrophy (cardiac weight index: 5.7 vs 5.2, 5.0, 4.9mg/g) and fibrosis (25.3 vs 8.9, 12.6, 12.5%) (all P<0.05). The anti-hypertrophic effect of SCFAs were mediated via cognate SCFA receptors GPR43/GPR109A (wild-type cardiac weight index 4.53 vs 6mg/g, 11.9% vs 24.4% perivascular fibrosis, P<0.01). Fibre increased the abundance of splenic T regulatory (Treg) cells (control 4.3 vs 6.2%, P<0.001) and acetate (4.3 vs 5.1, P=0.02). Conclusions: Lack of prebiotic dietary fibre leads to the development of a hypertensinogenic gut microbiome, hypertension and its complications. SCFA might represent new therapeutic opportunities through modulation of G-coupled protein receptors and Treg cells.