Association between gut dysbiosis and neurogenic diseases, such as hypertension, has been described. The aim of this study was to investigate whether changes in the gut microbiota alter gut-brain interactions inducing changes in blood pressure (BP). Recipient normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were orally gavaged with donor fecal contents from SHR and WKY. We divided the animals into four groups: WKY transplanted with WKY microbiota (W-W), SHR with SHR (S-S), WKY with SHR (W-S) and SHR with WKY (S-W). Basal systolic BP (SBP) and diastolic BP (DBP) were reduced with no change in heart rate as a result of fecal microbiota transplantation (FMT) from WKY rats to SHR. Similarly, FMT from SHR to WKY increased basal SBP and DBP. Increases in both NADPH oxidase-driven reactive oxygen species production and proinflammatory cytokines in brain paraventricular nucleus linked to higher BP drop with pentolinium and plasmatic noradrenaline (NA) levels were found in the S-S group as compared to the W-W group. These parameters were reduced by FMT from WKY to SHR. Increased levels of pro-inflammatory cytokines, tyrosine hydroxylase mRNA levels and NA content in the proximal colon, whereas reduced mRNA levels of gap junction proteins, were found in the S-S group as compared to the W-W group. These changes were inhibited by FMT from WKY to SHR. According to our correlation analyses, the abundance of Blautia and Odoribacter showed a negative correlation with high SBP. In conclusion, in SHR gut microbiota is an important factor involved in BP control, at least in part, as consequence of its effect on neuroinflammation and the sympathetic nervous system activity.

Aim: High blood pressure (BP) is associated with gut microbiota dysbiosis. The aim of this study was to investigate whether changes in gut microbiota induced by exchanging the gut microbiota between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) alter the gut-immune system interaction inducing changes in vascular function and BP. Methods: Twenty-week-old recipient WKY and SHR were orally gavaged with donor faecal contents from WKY or SHR. In additional experiments, we used a design to determine whether blockade of B7-dependent costimulation with CTLA4-Ig or blockade of IL-17 with IL-17-neutralizing antibody could prevent hypertension caused by faecal microbiota transplantation (FMT) from SHR to WKY. Results: Correlation analyses identified the bacterial abundance of Turicibacter and S24-7_g that, respectively, positively and negatively correlated with systolic BP. FMT from WKY rats to SHR rats reduced basal systolic BP, restored the imbalance between Th17/Treg in mesenteric lymph nodes (MLNs) and aorta, and improved endothelial dysfunction and vascular oxidative status found in SHR transplanted with SHR faeces. FMT from SHR to WKY increased CD80 and CD86 mRNA levels and T cells activation in MLNs, circulating T cells, aortic T cell infiltration, impaired endothelial function and increased basal SBP. These effects were abolished by blockade of B7-dependent costimulation with CTLA4-Ig. IL-17a neutralizing antibody reduced SBP and improved endothelial dysfunction induced by FMT from SHR to WKY. Conclusion: Gut microbiota is an important factor involved in the control of BP, as a consequence of its effect in T-cell activation in gut immune system and vascular T-cells accumulation. K E Y W O R D S endothelial dysfunction, gut dysbiosis, hypertension, immune cells See Editorial Commentary: Durgan, D. J. 2019. Evidence for a gut-immune-vascular axis in the development of hypertension.

Scope The objective of this study is to determine the cardiovascular effects of the probiotics Bifidobacterium breve CECT7263 (BFM) and Lactobacillus fermentum CECT5716 (LC40), and the short chain fatty acids butyrate, and acetate in spontaneously hypertensive rats (SHR). Methods and results Ten five‐week old Wistar Kyoto rats (WKY) and fifty aged‐matched SHR are randomly distributed into six groups: control WKY, control SHR, treated SHR‐LC40, treated SHR‐BMF, treated SHR‐butyrate, and treated SHR‐acetate. Chronic treatments with LC40 or BFM increase butyrate‐producing bacteria and prevent the blood pressure increase in SHR. Oral treatment with butyrate or acetate also prevents the increase in both blood pressure and Firmicutes/Bacteroidetes (F/B) ratio. All treatments restore the Th17/Treg balance in mesenteric lymph nodes, normalized endotoxemia, and prevent the impairment of endothelium‐dependent relaxation to acetylcholine, as a result of reduced NADPH oxidase‐driven reactive oxygen species production. These protective effects might be mediated by both the reduction in vascular lipopolysaccharide (LPS)/toll‐like receptor 4 (TLR4) pathway and the increase in Treg infiltration in the vasculature. Conclusion The probiotics LC40 and BFM prevent dysbiosis and the development of endothelial dysfunction and high blood pressure in genetic hypertension. These effects seem to be related to endotoxemia reduction and to increase Treg accumulation in the vasculature.

Probiotics exert cardiovascular protective effects in genetic hypertension related to the improvement of vascular pro-oxidative and pro-inflammatory status.

Obesity is associated with intestine dysbiosis and is characterized by a low-grade inflammatory status, which affects vascular function. In the present study, we evaluated the effects of a probiotic with immunomodulatory properties, Lactobacillus coryniformis CECT5711, in obese mice fed on an HFD (high-fat diet). The probiotic treatment was given for 12 weeks, and it did not affect the weight evolution, although it reduced basal glycaemia and insulin resistance. L. coryniformis administration to HFD-induced obese mice induced marked changes in microbiota composition and reduced the metabolic endotoxaemia as it decreased the LPS (lipopolysaccharide) plasma level, which was associated with a significant improvement in gut barrier disruption. Furthermore, it lowered TNFα (tumour necrosis factor α) expression in liver, improving the inflammatory status, and thus the glucose metabolism. Additionally, the probiotic reversed the endothelial dysfunction observed in obese mice when endothelium- and NO (nitric oxide)-dependent vasodilatation induced by acetylcholine in aortic rings was studied. It also restored the increased vessel superoxide levels observed in obese mice, by reducing NADPH oxidase activity and increasing antioxidant enzymes. Moreover, chronic probiotic administration for 2 weeks also improved endothelial dysfunction and vascular oxidative stress induced by in vivo administration of LPS in control mice fed on a standard chow diet. The results of the present study demonstrate an endothelial-protective effect of L. coryniformis CECT5711 in obese mice by increasing NO bioavailability, suggesting the therapeutic potential of this gut microbiota manipulation to prevent vasculopathy in obesity.