Critical Role of the Interaction Gut Microbiota – Sympathetic Nervous System in the Regulation of Blood Pressure

Abstract

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.

Changes to the gut microbiota induced by losartan contributes to its antihypertensive effects

“…The FMT to recipient rats was performed as previously reported (Toral et al, , ). Faecal contents were diluted 1:20 in sterile PBS and centrifuged at 60 g for 5 min.…”

“…Recently, it has been demonstrated that the normal gut microbiota may influence BP. A direct association between gut microbiota and hypertension in both animal models and humans has been described (Yang et al, ; Kim et al, , Toral et al, , , Sun et al, ). In contrast, Karbach et al () showed that BP was not different between germ‐free and conventionally raised mice, which is consistent with previous observations describing no effect on BP after dramatic reduction in faecal microbial biomass induced by antibiotic treatment (Pluznick et al, ).…”

“…Similarly, both the Firmicutes/Bacteroidetes (F/B) ratio and the abundance levels of selected genera in pre‐hypertensive spontaneously hypertensive rats (SHR) were not significantly different from the age matched Wistar Kyoto rats (WKY) (Santisteban et al, ). Interestingly, transplantation of microbiota from SHR to WKY (Adnan et al, ; Toral et al, ) or from hypertensive humans to germ‐free mice (Li et al, ) increased BP, showing the role of dysbiotic microbiota in the development of hypertension. In humans, overgrowth of bacteria such as Prevotella and Klebsiella has been described in both pre‐hypertensive and hypertensive populations, compared with levels in healthy subjects (Li et al, ).…”

“…Moreover, systolic BP (SBP) positively correlated with six bacterial species ( Parabacteroides johnsonii , Klebsiella unclassified , Anaerotruncus unclassified , Eubacterium siraeum , Prevotella bivia , and Rumminococcus torques ) and negatively correlated with three ( Bacteroides thetaiotaomicron , Paraprevotella clara , and Paraprevotella unclassified ) species (Kim et al, ). In SHR, a strong positive correlation between SBP and the lactate‐producing genus Lactobacillus (Adnan et al, ), or Streptococcus and Turicibacter (Toral et al, ; Yang et al, ), and a negative correlation between butyrate‐producing bacteria genus Odoribacter and acetate‐producing bacteria genus Bautia with SBP (Toral et al, ) have been described. However, the absence of gut microbiota protects mice from angiotensin II‐induced hypertension, vascular dysfunction, and hypertension‐induced end‐organ damage, showing for the first time that commensal microbiota, an ecosystem acquired after birth, could represent an environmental factor promoting angiotensin II‐induced high BP (Karbach et al, ).…”

“…Normal microbiota regulates immune homeostasis, such as the balance between T helper 17 (Th17) and regulatory T cells (Treg) in gut lymph organs and in the vascular wall, which is involved in BP regulation (Karbach et al, ; Toral et al, ). Furthermore, a critical role of the interaction between the gut microbiota and the sympathetic nervous system in the regulation of BP has been recently described (Toral et al, , ). We hypothesised that BP reduction in established hypertension might contribute to correct gut dysbiosis in SHR, and might also contribute to maintain low BP through changed T cell populations in the vascular wall.…”