Exploring a Role for Gut Microbiota to Modulate Aldosterone
Authors: Moore Brittni N. , Medcalf Alexandra D. , Pluznick Jennifer L. 
Published: May 2024

Hypertension is associated with an increased risk of mortality for numerous conditions including heart disease, diabetes, and renal disease (D. Aune, Biomed Res Int, 2021). Hypertension is often viewed as idiopathic and treatment is seldom aimed at addressing an underlying mechanism; however, a recent study indicates that primary aldosteronism is an underappreciated cause of idiopathic hypertension (J. Brown, Ann Intern Med, 2020). Here, we investigate for the first time the influence of gut microbiota on aldosterone regulation. To pursue this, we used C57Bl/6 mice (n=20; males) housed in the Johns Hopkins Animal Care Facility and fed a specific pathogen-free diet. Whole blood from submandibular cheek bleeds were collected into K2EDTA-treated tubes at baseline and mice were allowed to recover. Mice were then treated with antibiotics (ABX; 1g/L ampicillin, 1g/L neomycin, and 0.5g/L vancomycin) in their drinking water ad libitum for a total of 7 days to dramatically suppress gut microbes. Whole blood via submandibular cheek bleeds were collected after 24hrs, and at day 7 on ABXs. Mice were sacrificed on day 7 of ABX. Plasma samples from baseline, 24hrs on ABX and 7 days on ABX were used to determine aldosterone concentration and plasma renin activity (PRA) via ELISA. In addition, 24hr urine samples were collected at baseline and at day 7 on ABXs. Statistics were calculated using paired, one-way ANOVA; data below are mean ± SD. Our results demonstrate that plasma aldosterone and PRA, as well as urine aldosterone, were significantly increased from baseline to 7 days on ABX treatment (plasma aldo (pg/mL): 295.1 ± 164.8 vs 634.9 ± 290.4, p= 0.0197; plasma PRA (ng Ang-1/mL/hr): 191.8 ± 137.6 vs 325.9 ± 141.5, p= 0.0108; urine aldo (pg/mL): 2019 ± 322.1 vs 2668 ± 292.0, p = 0.0047). However, there was no significant difference in plasma aldosterone from baseline to 24hrs on ABX treatment (295.1 ± 164.8 vs 434.5 ± 245.3, p= 0.1047). In contrast, we observed a significant increase in angiotensin I from baseline to 24hrs on ABX treatment (191.8 ± 137.6 vs 355.8 ± 139.6, p=0.0041), and this increase was sustained until day 7 (325.9 ± 141.5 vs baseline, p=0.0108). Preliminary data suggest aldosterone is also increased in the plasma of germ-free mice (without gut microbes) compared to conventionalized controls (750.4 ± 265.0, n= 6, vs 314.4 ± 260.3, n=4, p=0.0667), implying that gut microbiota normally act to suppress plasma aldosterone. Taken together, we demonstrate that in the absence of gut microbiota, plasma aldosterone, urine aldosterone, and PRA are significantly increased. Understanding how gut microbes influence aldosterone levels could provide valuable insights into the development and treatment of hypertension. This knowledge may open new avenues for therapeutic interventions, such as probiotics or dietary modifications, to help regulate blood pressure.

William Townsend Porter Predoctoral Fellowship from the American Physiological Society (BNM), Johns Hopkins Post-baccalaureate Research Education Program (PREP; R25GM109441 to ADM), the NIDDK Diabetic Complications Consortium (RRID:SCR_001415m www.diacomp.org, grants DK076169 and DK 115255 (subaward to JLP)) and American Heart Association Established Investigator Award (to JLP).

This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.