Abstract
BackgroundUrolithin A (UA) is produced by gut microflora from foods rich in ellagitannins. UA has been shown to improve mitochondrial health preclinically and in humans. Not everyone has a microbiome capable of producing UA, making supplementation with UA an appealing strategy.ObjectiveThis is the first detailed investigation of the prevalence of UA producers in a healthy population and the ability of direct UA supplementation to overcome both microbiome and dietary variability. Dietary intake of a glass of pomegranate juice (PJ) was used to assess UA producer status (n = 100 participants) and to characterize differences in gut microbiome between UA producers from non-producers.MethodsSubjects were randomized (1:1) to either PJ or a food product containing UA (500 mg). Prevalence of UA producers and non-producers were determined in the PJ group. Diet questionnaires and fecal samples were collected to compare differences between UA producers and non-producers along with plasma samples at different time points to assess levels of UA and its conjugates between the interventions.ResultsOnly 12% of subjects had detectable levels of UA at baseline. Following PJ intake ~40% of the subjects converted significantly the precursor compounds into UA. UA producers were distinguished by a significantly higher gut microbiome diversity and ratio of Firmicutes to Bacteroides. Direct supplementation with UA significantly increased plasma levels and provided a >6-fold exposure to UA vs. PJ (p < 0.0001).ConclusionsDifferences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation.
Highlights
ET are converted to ellagic acid (EA) in the upper portion of the human gastrointestinal tract, and further metabolized by gut microflora in the large intestine into compounds known as urolithins, of which Urolithin A (UA) is among the most common [2, 3]
The analysis showed that circulating levels of UA glucuronide were significantly higher (p < 0.0001; 2.4-fold higher mean level) with Mitopure supplementation compared with drinking pomegranate juice (PJ) (Fig. 4B)
All data are analyzed using a repeated measure ANOVA (A, C, E) and an unpaired t-test (B, D, F). This is the first study to compare the levels of exposure to UA obtained via natural dietary exposure to precursors vs. direct dietary supplementation with UA, and to evaluate the prevalence of natural UA producers across a significant sample size of a hundred healthy adults in a major metropolitan area in USA
Summary
This is the first detailed investigation of the prevalence of UA producers in a healthy population and the ability of direct UA supplementation to overcome both microbiome and dietary variability. Dietary intake of a glass of pomegranate juice (PJ) was used to assess UA producer status (n = 100 participants) and to characterize differences in gut microbiome between UA producers from non-producers. Diet questionnaires and fecal samples were collected to compare differences between UA producers and non-producers along with plasma samples at different time points to assess levels of UA and its conjugates between the interventions. Direct supplementation with UA significantly increased plasma levels and provided a >6-fold exposure to UA vs PJ (p < 0.0001). Conclusions Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation
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