Influence of exogenous dietary nitrate on downstream atherogenic metabolites of the enteral microbiome

Miriam Rinke (Essen)1, D. Messiha (Essen)1, A. Schultz Moreira Amos (Essen)1, J. Lortz (Essen)1, K. Hogrebe (Essen)1, J. Kehrmann (Essen)2, T. Rassaf (Essen)1, C. Rammos (Essen)1

1Universitätsklinikum Essen Klinik für Kardiologie und Angiologie Essen, Deutschland; 2Universitätsklinikum Essen Institut für Medizinische Mikrobiologie Essen, Deutschland



A growing body of data shows that the enteral microbiome influences cardiovascular diseases. Exogenous dietary nitrate mediates cardioprotective effects and has been shown to have an influence on the oral and enteral microbiome. The nutritional aspects of these cardioprotective effects are particularly intriguing since nitrate is abundant in our everyday diet.

Whether dietary nitrate influences the enteral microbiome and downstream metabolites like short chain fatty acids (SCFA) or trimethylamine N-oxide (TMAO) was investigated in the present study.



Aim of this study was to investigate the influence of dietary anorganic nitrate intake on the enteral microbiome composition and atheroscleorsis-associated metabolites in a healthy trial cohort.



We recruited a group of 30 healthy patients who were divided into two cohorts. For 30 days, one cohort received dietary nitrate (0, 12 mmol/kg bodyweight) while the other cohort received equimolar dietary sodium chloride as a placebo. 

We collected blood and stool samples at baseline and after 30 days, as well as measurements of vascular markers, such as pulse wave velocity (PWV) and ankle brachial index (ABI). 16S-rRNA was sequenced from stool samples to analyse microbiome composition, as well as downstream metabolites, such as TMAO in serum samples at baseline and follow-up. 



We detected a distinct regulation in enteral microbiome composition after dietary nitrate supplementation with decreased abundance of the gram-negative bacteria Akkermansia and Verrucomicrobia, which is associated with higher TMAO levels. There was no significant difference between the two groups after nitrate and placebo supplementation in the shannon diversity (p > 0.05). The relative abundance of gram-positive clostridiaceae in the verum group was higher than in the placebo group, which are also associated with higher TMAO levels. Correspondingly, levels of the downstream metabolite TMAO significantly increased after dietary nitrate supplementation (placebo follow up 343,88 m/L vs nitrate follow-up 481,15 m/L p < 0.05).

While the dietary nitrate supplementation had no influence on vascular parameters like PWV in our healthy cohort (placebo follow up 7,57 m/s vs nitrate follow up 7,5 m/s, p > 0.05), we were able to demonstrate that the systolic blood pressure in the nitrate group significantly decreased (baseline 124,73 mmHg vs follow up 120 mmHg, p < 0.05).



In conclusion our results indicate that dietary anorganic nitrate supplementation has an influence on microbiome composition and correspondingly on downstream atherogenic metabolites such as TMAO. Further ongoing analysis will help identify the mechanisms behind those correlations and the clinical relevance of those findings in a cardiovascular diseased cohort.

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