Abstract P156: Fiber-rich Diet Suppresses Lactobacillus And Increases Blood Pressure In The Shr Independently Of T-lymphocyte Immune Responses

Abstract

Introduction: Gut dysbiosis has been linked to hypertension in both rodents and humans. Microbial metabolites such as propionate have been shown to regulate blood pressure (BP), while butyrate, one of the major fermented end-products of fiber, reportedly produces beneficial anti-inflammatory effects in multiple dysbiosis-related diseases. Therefore, we tested the impact of a fiber-rich, butyrolytic diet on BP regulation and immune responses in the spontaneously hypertensive rats (SHR). Methods: SHR (5 wo) were placed on either the fructooligosaccharides/inulin-rich diet (Fiber, N=6), or its calorie-matched control diet (Control, N=6) (Research Diets, Inc.) for 10 weeks. Baseline BP was measured by tail cuff every week for the duration of the study. Fecal samples were collected for HPLC analysis of butyrate, and Lactobacillus population by QPCR. Manganese-enhanced magnetic resonance imaging was used to monitor neural activity in cardioregulatory brain regions. Blood was analyzed for circulating lymphocyte populations previously implicated in BP control in the SHR (CD3 + CD45 + , CD4 + CD25 + , CD8 + ). Results: Fiber-rich diet produced an increase in fecal butyrate levels as early as five weeks (Control vs. Fiber, 4.9umol/g vs. 9.7umol/g, p=0.068, N=6). This was associated with contraction of fecal Lactobacillus (47.5% vs. 5.9%, p=0.0008, N=6). However, we observed significantly higher systolic BP (181.4mmHg vs. 201.7 mmHg, p=0.0088, N=6) in the fiber group compared with control, beginning with week 9 post-diet switch. Changes in neural activation were observed in the paraventricular nucleus of hypothalamus (PVN) (3.3 voxel vs. 7.3 voxel, p=0.26) and amygdala (93.3 voxel vs. 31 voxel, p=0.0059, N=3). No changes in circulating T-lymphocytes were observed between the two groups: CD3 + CD45 + (32.4% vs. 32.1% lymphocytes); CD4 + CD25 + (1.05% vs. 0.78% lymphocytes); CD8 + (18.7% vs. 16.2% lymphocytes, N=6) at week 10 post-diet switch. Conclusion: Fiber-rich diet suppression of Gut Lactobacillus is associated with increase in BP in the SHR, independently of T-lymphocyte responses. The observed higher neural activity in PVN and lower in amygdala in the fiber group suggest direct effects of gut bacterial metabolites on brain cardioregulatory regions.