Metabolism of different dietary phenolic compounds by the urolithin-producing human-gut bacteria Gordonibacter urolithinfaciens and Ellagibacter isourolithinifaciens.

Rocío García-Villalba,María D Frutos,Juan C Espín,María V Selma,Francisco A Tomás-Barberán,David Beltrán

doi:10.1039/d0fo01649g

Abstract

Gordonibacter urolithinfaciens and Ellagibacter isourolithinifaciens are two human gut bacterial species that convert ellagic acid into urolithins. Urolithins are bioactive postbiotics produced by dehydroxylation reactions catalyzed by different catechol-dehydroxylases. The metabolic ability of these anaerobic bacteria on other dietary-phenolic compounds is unknown. In the present study, we evaluated the metabolism of flavonoids (quercetin, hesperetin, hesperidin, nobiletin, catechin, isoxanthohumol), isoflavonoids (daidzein), coumarins (esculetin, umbelliferone, scoparone), phenylpropanoids [caffeic acid; 3-(3',4'-dihydroxyphenyl)propanoic acid (dihydrocaffeic acid); rosmarinic acid, and chlorogenic acid], benzoic acid derivatives (gallic acid, ellagic acid), lignans (secoisolariciresinol diglucoside), stilbenes (resveratrol), and secoiridoids (oleuropein) by G. urolithinfaciens DSM 27213T and E. isourolithinifaciens DSM 104140T. Both strains metabolized ellagic acid leading to the characteristic urolithins. They also metabolized caffeic, dihydrocaffeic, rosmarinic, and chlorogenic acids. The rest of the phenolic compounds were not transformed. Catechol dehydroxylation and double bond reduction were prominent transformations observed during the incubations. The enzymatic activities seem to have a narrow substrate scope as many catechol- (quercetin, catechin, esculetin, gallic acid) and double bond-containing (resveratrol, esculetin, scoparone, umbelliferone) phenolics were not metabolized. The catechol-dehydroxylase activity was more efficient in E. isourolithinifaciens, while the reductase activity was more relevant in G. urolithinfaciens.

Highlights

The bioavailability of dietaryphenols (PPs) is very low.[1]
In the case of ellagitannins and ellagic acid, the original PPs are converted to urolithins,[6] and different metabolites are produced by the opening and decarboxylation of one of the two lactone rings in the ellagic acid molecule and the sequential removal of phenolic hydroxyls that lead to different urolithin metabolites.[7]
We aimed to evaluate the metabolism of eighteen dietary phenolics, representative of different phenolic classes, by G. urolithinfaciens and E. isourolithinifaciens, and identify the metabolites produced

Summary

Introduction

The bioavailability of dietary ( poly)phenols (PPs) is very low.[1]. Most of them reach the colon where they are catabolized by the gut microbes producing metabolites, recently named as postbiotics,[2,3,4] that are much better absorbed than the original PPs, show relevant biological effects in the colon and systemically, and persist in the body for long periods (sometimes up to three or four days).[5]In the case of ellagitannins and ellagic acid, the original PPs are converted to urolithins,[6] and different metabolites are produced by the opening and decarboxylation of one of the two lactone rings in the ellagic acid molecule and the sequential removal of phenolic hydroxyls that lead to different urolithin metabolites.[7]. Three consistent metabotypes for the production of urolithins have been reported in humans,[8] and bacterial strains producing this metabolic conversion have been discovered, characterized, and deposited in bacterial banks. Gordonibacter urolithinfaciens and Gordonibacter pamelaeae, the first bacterial species that were reported to produce urolithins from ellagic acid, were able to provide urolithins M5 (3,4,8,9,10-pentahydroxy urolithin), M6 (3,8,9,10-tetrahydroxy urolithin) and C (3,8,9-trihydroxy urolithin),[9,10] and the abundance of this genus within a complex human gut bacterial community positively correlated with the metabotype A, while correlated negatively with metabotype B.11. The recently discovered Ellagibacter isourolithinifaciens[12,13] was able to produce isourolithin A (3,9-dihydroxy urolithin) and positively correlated with metabotype B.14 Gordonibacter urolithinfaciens and Gordonibacter pamelaeae, the first bacterial species that were reported to produce urolithins from ellagic acid, were able to provide urolithins M5 (3,4,8,9,10-pentahydroxy urolithin), M6 (3,8,9,10-tetrahydroxy urolithin) and C (3,8,9-trihydroxy urolithin),[9,10] and the abundance of this genus within a complex human gut bacterial community positively correlated with the metabotype A, while correlated negatively with metabotype B.11 the recently discovered Ellagibacter isourolithinifaciens[12,13] was able to produce isourolithin A (3,9-dihydroxy urolithin) and positively correlated with metabotype B.14

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