Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population

• Published in: European journal of clinical nutrition Vol. 76; no. 2; pp. 297 - 308
• Main Authors: Singh, Anurag, D’Amico, Davide, Andreux, Pénélope A., Dunngalvin, Gillian, Kern, Timo, Blanco-Bose, William, Auwerx, Johan, Aebischer, Patrick, Rinsch, Chris
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2022; Nature Publishing Group
• Subjects: 692/308/575; 692/53; Adult; Age groups; Clinical Nutrition; Coumarins - pharmacology; Diet; Dietary Exposure; Dietary intake; Dietary Supplements; Digestive system; Epidemiology; Exposure; Feces; Food; Food intake; Fruits; Gastrointestinal Microbiome; Gut microbiota; Humans; Internal Medicine; Intestinal microflora; Investigations; Laboratories; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolites; Microbiomes; Microbiota; Mitochondria; Nutrition research; Nuts; Plasma levels; Population; Public Health; Questionnaires
• ISSN: 0954-3007; 1476-5640; 1476-5640
• DOI: 10.1038/s41430-021-00950-1

Background Urolithin 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. Objective 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. Methods Subjects 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. Results Only 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). Conclusions Differences in gut microbiome and diet that dictate natural exposure to UA can be overcome via direct dietary UA supplementation.