Antibiotics attenuate experimental hypertension in rats

Honour, JW; Borriello, S. P.; Ganten, Ursula; Honour, Pauline

doi:10.1677/joe.0.1050347

Cited by 31 publications

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“…Although numerous articles have speculated or discussed a potential role for gut dysbiosis in the development of other cardiovascular diseases, relatively few studies have addressed this issue directly. Several animal models of hypertension and a small cohort of humans suggests that gut dysbiosis is associated with hypertension (16,17,23,33). Durgan et al (8) demonstrated a causal role of the gut microbiota in the development of obstructive sleep apnea-induced hypertension in rats fed a high-fat diet.…”

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Alterations in the gut microbiota can elicit hypertension in rats

Adnan

Nelson

Ajami

et al. 2017

Physiological Genomics

320

284

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Gut dysbiosis has been linked to cardiovascular diseases including hypertension. We tested the hypothesis that hypertension could be induced in a normotensive strain of rats or attenuated in a hypertensive strain of rats by exchanging the gut microbiota between the two strains. Cecal contents from spontaneously hypertensive stroke prone rats (SHRSP) were pooled. Similarly, cecal contents from normotensive WKY rats were pooled. Four-week-old recipient WKY and SHR rats, previously treated with antibiotics to reduce the native microbiota, were gavaged with WKY or SHRSP microbiota, resulting in four groups; WKY with WKY microbiota (WKY g-WKY), WKY with SHRSP microbiota (WKY g-SHRSP), SHR with SHRSP microbiota (SHR g-SHRSP), and SHR with WKY microbiota (SHR g-WKY). Systolic blood pressure (SBP) was measured weekly using tail-cuff plethysmography. At 11.5 wk of age systolic blood pressure increased 26 mmHg in WKY g-SHRSP compared with that in WKY g-WKY (182 ± 8 vs. 156 ± 8 mmHg, = 0.02). Although the SBP in SHR g-WKY tended to decrease compared with SHR g-SHRSP, the differences were not statistically significant. Fecal pellets were collected at 11.5 wk of age for identification of the microbiota by sequencing the 16S ribosomal RNA gene. We observed a significant increase in the Firmicutes:Bacteroidetes ratio in the hypertensive WKY g-SHRSP, as compared with the normotensive WKY g-WKY ( = 0.042). Relative abundance of multiple taxa correlated with SBP. We conclude that gut dysbiosis can directly affect SBP. Manipulation of the gut microbiota may represent an innovative treatment for hypertension.

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confidence: 99%

Alterations in the gut microbiota can elicit hypertension in rats

Adnan

Nelson

Ajami

et al. 2017

Physiological Genomics

320

284

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“…DOC can 276 also be transformed by gut flora to progesterone metabolites 277[19,21]; these progesterone metabolites (which are not 11-oxy-278 genated) do not inhibit either of the two 11b-HSD isoforms.279 Administration of the antibiotic, neomycin, blocks the formation280 of these metabolites of corticosterone in the intestine, interrupting 281 the enterohepatic recirculation of these products, and blunts the 282 increase in blood pressure observed in rats infused with either 283 ACTH or corticosterone[65]. Similar effects of neomycin have also284 been demonstrated in other selected rat models of experimental 285 hypertension[66,67]. Thus, in rats, 5a-pathway products of corti-286 costerone and the 11-oxygenated progesterone derivatives, can 287 play a role to prolong the lifespan, t 1/2 , of corticosterone in the 288 circulation and in target tissues.…”

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Why do humans have two glucocorticoids: A question of intestinal fortitude

Morris

2015

Steroids

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“…The first results were presented at a Serono Symposium: Endocrinology of Hypertension, Padua, Italy, in October 1981 (18), the 164th meeting of the Society for Endocrinology (19), and at the Sixth International Congress on Hormonal Steroids, Jerusalem, Israel, in September 1982 (21). Hypertension was prevented by prior treatment of the rats with neomycin (22,24); vancomycin had a weaker effect (24). Neomycin also slowed the development of hypertension in a spontaneously hypertensive rat of stroke-prone substrain (24).…”

Section: Steroid Hypertension In the Ratmentioning

confidence: 99%

“…Hypertension was prevented by prior treatment of the rats with neomycin (22,24); vancomycin had a weaker effect (24). Neomycin also slowed the development of hypertension in a spontaneously hypertensive rat of stroke-prone substrain (24). The gut bacteria were examined with conventional techniques at that time.…”

Section: Steroid Hypertension In the Ratmentioning

confidence: 99%

“…I would like to draw to the attention of the readers a historical foundation, from more than 30 years ago, to such associations with hypertension. Observations in humans of the enterohepatic circulation of corticosterone (17) were taken further with studies in rats (18,19,21,22,24) where the experimental increase of blood pressure through the action of steroids was prevented by administration of antibiotics.…”

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Historical perspective: gut dysbiosis and hypertension

Honour

2015

Physiological Genomics

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AN ENORMOUS NUMBER OF MICROBES populate external and internal surfaces of humans influencing a variety of aspects of host physiology such as providing nutrients and vitamins. The microbiome influences Phase I and Phase II drug metabolism (43) . In recent years, a number of studies have pointed to links between the gut microbiota and pathophysiology of diabetes (8, 36), cancer (27), bowel disorders (9, 15), liver disease (46), immune conditions (33), and the metabolic syndrome (12). Increased understanding of these processes may unravel tremendous potential for therapeutics. Gut microbiota can influence a number of processes that affect the control of blood pressure.Interesting studies linking gut microbiota with hypertension in the Dahl rat have been reported in this journal by Mell and colleagues (28). The cecal contents of salt-sensitive (S) rats were significantly different to salt-resistant (R) rats. To test further if differences in microbiota contribute to the extent of blood pressure regulation, microbial transplantation experiments were performed. The hypertension of S rats was exacerbated when the S rats were given R rat microbiota. Another recent publication (47) showed an altered gut microbiota in spontaneously hypertensive rats (SHR) compared with Wistar Kyoto (WKY) rat models and a small cohort of hypertensive patients. They claimed an association of gut dysbiosis with hypertension. I would like to draw to the attention of the readers a historical foundation, from more than 30 years ago, to such associations with hypertension. Observations in humans of the enterohepatic circulation of corticosterone (17) were taken further with studies in rats (18,19,21,22,24) where the experimental increase of blood pressure through the action of steroids was prevented by administration of antibiotics. Clinical Evidence for Enterohepatic Circulation of SteroidsIntestinal metabolism was described in studies of humans with a rare disorder of synthesis of cortisol and sex steroids due to a genetic defect of steroid cytochrome 17-hydroxylase (CYP17), a condition defined by Biglieri et al. in 1966 (2). The hypertension in such patients is attributed to excess production of deoxycorticosterone, which causes renal sodium retention (see Fig. 1 for pathways of steroid synthesis). Plasma renin activity is suppressed and aldosterone production low. The urinary steroid metabolome of this condition was described in 1978 (17). Among the steroid metabolites of corticosterone were a high proportion of 21-deoxycorticosterone steroids. In a tracer experiment the 21-deoxy steroids retained the radiaoctive label of injected corticosterone (38). When steroid production in a CYP17-deficient patient was stimulated with adrenocorticotrophic hormone (ACTH) or suppressed with dexamethasone, the changes in corticosterone metabolites with 21-hydroxyl groups preceded the changes of the 21-deoxycorticosterone products by 1 or 2 days (20). These observations mimicked changes in corticosterone metabolism of germ-free rats that did not produce the...

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Antibiotics attenuate experimental hypertension in rats

Cited by 31 publications

References 0 publications

Alterations in the gut microbiota can elicit hypertension in rats

Alterations in the gut microbiota can elicit hypertension in rats

Why do humans have two glucocorticoids: A question of intestinal fortitude

Historical perspective: gut dysbiosis and hypertension

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