Metabolic fate of ellagitannins in human gut microbiota ex vivo cultures

Ellagitannin-rich plant materials are used as popular remedies in the treatment of various inflammatory diseases. Due to the questionable bioavailability of ellagitannins nowadays their gut microbiota metabolites-urolithins are claimed to be responsible for the observed health effects. Various medicinal plants as well as food products were established to be a source of urolithins [1,2]; however studies conducted on pure ellagitannin compounds metabolism are still remaining scarce. The aim of the study was to examine the metabolic fate of selected ellagitannins using ex vivo cultures of human gut microbiota. Thirteen monomeric and dimeric ellagitannins (pedunculagin, vescalagin, castalagin, agrimoniin, stachyurin, casuarinin, oenothein B, gemin A, 1-O-galloyl-4,6-(S)-HHDP-β-D-glucose, potentillin, coriariin, casuarictin, stenophyllin) together with ellagic acid were chosen for examination. The formation of metabolites in a culture media inoculated with human faecal samples was monitored after 24 and 48 hours using UHPLC-DAD-MS/MS method. Additionally the quantitative analysis of most abundant metabolites: 3,8-dihydroxyurolithin (UA), 3,9-dihydroxyurolithin (IUA) and 3-hydroxyurolithin (UB) was conducted by UHPLC-DAD method. Only ellagitannins possessing the hexahydroxydiphenoyl moiety were metabolised in ex vivo microbiota cultures to dibenzo [b,d]pyrane-6-one derrivatives – urolithins. After 24h dominating products of the metabolism were urolithins with 3 – 4 hydroxyl groups (urolithin C and M6 together with their isomers). Further 24h incubation led to their subsequent dehydroxylation to UA and/or IUA. Production rate of UA was most abundant in the case of pedunculagin: from 10 to 0.58µM UA and the lowest in the case of ellagic acid: 0.08µM UA. Thus, when peroral use of medicinal plant materials and food products containing ellagitannins with HHDP group is considered, the formation of urolithins has to be referred and reference to their bioactivity needs to be addressed.

Keywords: ellagitannis, urolithins, gut microbiota.

References:

[1] Espín JC, Larrosa M, García-Conesa MT, Tomás-Barberán F. Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far. Evid Based Complement Altern Med 2013; 2013: 270418

[2] Piwowarski JP, Granica S, Zwierzynska M, Stefanska J, Schopohl P, Melzig MF, Kiss AK. Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials. J Ethnopharmacol 2014; 155: 801 – 809