Alterations in the gut microbiota can elicit hypertension in rats
Authors: Nelson Jimmy , Adnan Sareema , Ajami Nadim , Petrosino Joseph , Bryan Robert , Durgan David 
Published: November 2023

GI dysbiosis, or alterations in the gut microbiome, is associated with many different cardiovascular diseases including hypertension. Thus we hypothesized that this imbalance in bacterial populations could directly contribute to the development of hypertension. In order to test this hypothesis we sought to induce hypertension in a normotensive strain of rat (WKY) and abolish hypertension in a spontaneously hypertensive strain of rat (SHR) through transplantation of gut microbiota. We pooled both SHR and WKY cecal content separately, containing microbiota representative of each strain, and orally gavaged this content into 4‐week‐old WKY and SHR animals that had undergone treatment with antibiotics to rid their GI tract of their native microbial populations. After the gavages of cecal content were administered, we were left with four groups of animals, WKY strain with WKY microbiota (WKY g‐WKY), WKY strain with SHR microbiota (WKY g‐SHR), SHR strain with WKY microbiota (SHR g‐WKY) and finally SHR strain with SHR microbiota (SHR g‐SHR) with n=7 per group. Using tail cuff plethysmography, we monitored systolic blood pressure (SBP) weekly. at 11.5 weeks of age systolic blood pressure was elevated 26 mmHg in WKY g‐SHR compared to that in WKY g‐WKY (182 ± 8 versus 156 ± 8 mmHg respectively, p=0.02). SBP in SHR g‐WKY tended to be lower than SHR g‐SHR rats, but this decrease did not reach statistical significance. Fecal pellets were collected weekly to identify microbiota present in the GI tract of each animal using 16s rRNA gene sequencing. Fecal pellets from animals at 11.5 weeks of age were sequenced. we discovered that microbiota were successfully transplanted and that WKY animals gavaged with SHR cecal content showed significant changes in their GI microbiota when compared to the WKY animals gavaged with WKY content. WKY g‐SHR animals showed an increase in the Firmicutes:Bacteroidetes (F:B) ratio (p=.042) in comparison with the normotensive WKY g‐WKY animals; this ratio is a representative of dysbiosis and observed in many diseases associated with pathological dysbiosis. Along with the increase in F:B ratio the hypertensive WKY g‐SHR animals also experienced increases in bacterial populations that produce lactate and decreases in populations of bacteria that produce beneficial short‐chain fatty acids (SCFA). To further test our hypothesis, we also used a cross‐fostering protocol to introduce SHR microbiota to WKY animals and vice versa. Given that rodent microbiota composition most closely mimics the nursing mother, we fostered 1–2 day old WKY and SHR pups on mothers of the opposite strain and measured BP from 6–14 weeks. Mirroring the results from our previous study, at 14 weeks SBP increased in WKY rats fostered on SHR mothers by 32 mmHg when compared to their littermates kept with their birth mother (184 ± 6 versus 152 ± 5 mmHg respectively, p=0.003) From these studies we have concluded that GI microbiota can directly affect SBP and induce hypertension. Furthermore, the microbiome should be given more attention in the treatment of cardiovascular disease.

Support or Funding Information

AHA Predoctoral Fellowship 16PRE29640005 and IMBS Program T32 Training Grant 2T32GM008231‐26