Description of urolithin production capacity from ellagic acid of two human intestinal Gordonibacter species

Abstract

Ellagitannin and ellagic acid metabolism to urolithins in the gut shows a large human interindividual variability and this has been associated with differences in the colon microbiota. In the present study we describe the isolation of one urolithin-producing strain from the human faeces of a healthy volunteer and the ellagic acid transformation to different urolithin metabolites by two species of intestinal bacteria. The isolate belongs to a new species described as Gordonibacter urolithinfaciens, sp. nov. The type strain of the Gordonibacter genus, Gordonibacter pamelaeae DSM 19378(T), was also demonstrated to produce urolithins. Both human intestinal bacteria grew similarly in the presence and absence of ellagic acid at 30 μM concentration. Ellagic acid catabolism and urolithin formation occurred during the stationary phase of the growth of the bacteria under anaerobic conditions. The HPLC-MS analyses showed the sequential production of pentahydroxy-urolithin (urolithin M-5), tetrahydroxy-urolithin (urolithin M-6) and trihydroxy-urolithin (urolithin C), while dihydroxy-urolithins (urolithin A and isourolithin A), and monohydroxy-urolithin (urolithin B) were not produced in pure cultures. Consequently, either other bacteria from the gut or the physiological conditions found in vivo are necessary for completing metabolism until the final urolithins (dihydroxy and monohydroxy urolithins) are produced. This is the first time that the urolithin production capacity of pure strains has been demonstrated. The identification of the urolithin-producing bacteria is a relevant outcome as urolithin implication in health (cardiovascular protection, anti-inflammatory and anticarcinogenic properties) has been supported by different bioassays and urolithins can be used in the development of functional foods and nutraceuticals. This study represents an initial work that opens interesting possibilities of describing enzymatic activities involved in urolithin production that can help in understanding both the human interindividual differences in polyphenol metabolism, the microbial pathways involved, and the role of polyphenols in human health. The presence of urolithin producing bacteria can indirectly affect the health benefits of ellagitannin consumption.

Application of in vitro gastrointestinal digestion and colonic fermentation models to pomegranate products (juice, pulp and peel extract) to study the stability and catabolism of phenolic compounds

“…Although detected in control (i), coumaric and protocatechuic acid concentration increased after incubation. In contrast to the generation of urolithins, catechol, gallic acid, coumaric acid and protocatechuic acid production did not show considerable interindividual variability, which is probably related to the nonspecific bacteria needed for the precursor's degradation, as required for the conversion of ellagic acid into urolithins (Selma, Beltrán, García-Villalba, Espín, & Tomás-Barberán, 2014).…”

New insights into the bioavailability of red raspberry anthocyanins and ellagitannins

“…It has been reported that two human intestinal Gordonibacter species, G. urolithinfaciens and G. pamelaeae are able to convert ellagitannins and ellagic acid-derived compounds to urolithins [32]. Thus, biological activities ascribed to ellagitannin-rich foods, such as anti-inflammatory and anti-carcinogenic properties [33,34], may differ substantially depending on an individual's gut microbiota.…”

Gut microbiota modulation of chemotherapy efficacy and toxicity

“…Ellagic acid, a product of dietary polyphenols found in certain fruits, walnuts and wines, is metabolised by the gut microbiota to release urolithins 82 . Urolithin A is purported to have anti-proliferative effects in human colon cancer cells, mediating cell cycle arrest 83 , and co-treatment in vitro with urolithin A potentiates the effects of 5-FU and its pro-drug intermediate 5'DFUR 84 .…”