The Effect of Salt And Enalapril on Gut Bacteria Composition And Blood Level of Gut Bacteria‐derived Cardiovascular Markers
Authors: Ufnal Marcin , Bielinska Klaudia , Konop Marek , Radkowski Marek , Grochowska Marta , Perlejewski Karol , Huc Tomasz , Motooka Daisuke , Nakamura Shota 
Published: June 2021

Research suggests that gut bacterial metabolites such as trimethylamine N‐oxide (TMAO) and indoxyl sulfate affect the circulatory system homeostasis in mammals. However, the mechanisms are obscured. High‐salt diet is considered a cardiovascular risk factor, whereas treatment with ACE‐inhibitors such as enalapril reduces cardiovascular risk. We evaluated the effect of high salt intake and enalapril treatment on gut bacteria composition and plasma level of TMAO and indoxyl sulfate. In addition, hemodynamic effects of TMAO and indoxyl sulfate (indoxyl) were tested.

12–14‐week‐old, male, Wistar rats were maintained either on water (controls), or NaCl water solution (0.9 % or 2%), or enalapril water solution (50mg/l or 100mg/l) for two weeks. Blood plasma, urine and stools were analyzed for the concentration of TMA (TMAO‐precursor), TMAO, and indoxyl. Gut bacteria composition was analyzed with 16S rRNA gene sequence analysis. The gut‐blood barrier (GBB) permeability to TMA was assessed at baseline and after TMA intracolonic challenge test. Mean arterial blood pressure (MABP) and heart rate (HR) were recorded in controls at baseline and after the administration of either a vehicle, TMAO or indoxyl into the femoral vein (IV) or into the lateral ventricle of the brain (ICV).

Rats on high‐salt intake showed a significantly higher plasma TMAO and lower 24hr TMAO urine excretion than controls. In contrast, rats treated with enalapril showed significantly lower plasma TMAO and higher 24hr TMAO urine excretion than controls. TMA stool level was similar between the groups. There was no significant difference between the groups in the GBB permeability and TMA. Plasma indoxyl concentration and 24hr urine indoxyl excretion were similar between the groups. High salt intake, but not enalapril treatment changed gut bacteria composition. Specifically, we found a significant difference between controls and rats on high‐salt intake in 21 bacterial genera.

Vehicle and TMAO infused IV and ICV did not affect hemodynamics. In contrast, indoxyl infused IV produced a dose dependent increase in MABP and HR, whereas indoxyl infused ICV did not affect MABP and HR. The hemodynamic effects of indoxyl were inhibited by pretreatment with ondansetron and pizotifen but not flupentixol, a serotonin receptor blockers.

Factors modifying cardiovascular risk such as high sodium intake and ACE‐inhibitors affect rat plasma level of TMAO and indoxyl, gut bacterial metabolites. High sodium diet affects gut bacteria composition. Indoxyl increases arterial blood pressure and heart rate. We propose that mechanisms modifying cardiovascular risk may include changes in blood concentration of gut bacterial metabolites.

Support or Funding Information

This work was supported by National Science Centre, Poland, grant no. 2016/21/B/NZ5/02544.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.