Pomegranate extract induces ellagitannin metabolite formation and changes stool microbiota in healthy volunteers

Abstract

The health benefits of pomegranate (POM) consumption are attributed to ellagitannins and their metabolites, formed and absorbed in the intestine by the microbiota. In this study twenty healthy participants consumed 1000 mg of POM extract daily for four weeks. Based on urinary and fecal content of the POM metabolite urolithin A (UA), we observed three distinct groups: (1) individuals with no baseline UA presence but induction of UA formation by POM extract consumption (n = 9); (2) baseline UA formation which was enhanced by POM extract consumption (N = 5) and (3) no baseline UA production, which was not inducible (N = 6). Compared to baseline the phylum Actinobacteria was increased and Firmicutes decreased significantly in individuals forming UA (producers). Verrucomicrobia (Akkermansia muciniphila) was 33 and 47-fold higher in stool samples of UA producers compared to non-producers at baseline and after 4 weeks, respectively. In UA producers, the genera Butyrivibrio, Enterobacter, Escherichia, Lactobacillus, Prevotella, Serratia and Veillonella were increased and Collinsella decreased significantly at week 4 compared to baseline. The consumption of pomegranate resulted in the formation of its metabolites in some but not all participants. POM extract consumption may induce health benefits secondary to changes in the microbiota.

Strategies to promote abundance of Akkermansia muciniphila, an emerging probiotics in the gut, evidence from dietary intervention studies

“…Specifically, dietary supplementation of cranberry extract and Concord grape polyphenols increased A. muciniphila abundance in feces from 2% to over 30% (OTU sequences) and from 6.2% to 49.1% on the high-fat fed DIO mice, respectively (Anhê et al, 2015; Roopchand et al, 2015). Whereas the intake of pomegranate extract, green tea extract, and whole California table grape showed no effect on A. muciniphila abundance of healthy humans or DIO mice (Axling et al, 2012; Baldwin et al, 2016; Li et al, 2015). The inconsistent results suggest that the A. muciniphila -promoting effects of dietary polyphenols are highly depended on their chemical nature and sources.…”

“…Also, in the human study, although pomegranate extract did not change A. muciniphila abundance in the feces, the bacterium was 33-fold and 47-fold higher in stool samples of the subjects who are able to produce pomegranate metabolite urolithin as compared to non-producers at baseline and after 4 weeks dietary treatment, respectively. This suggested that A. muciniphila might play an important role in the breakdown of phenolic compounds in the intestine and specific group of humans may benefit more from polyphenols for promoting A. muciniphila (Li et al, 2015). In summary, since dietary polyphenols are so diverse and abundant, a validated in vitro SHIME model would be very helpful as a quick tool to screen and detect which polyphenols are effective in promoting A. muciniphila growth, then animal and human studies could be followed up for verifying their activities.…”

Role of the small intestine, colon and microbiota in determining the metabolic fate of polyphenols

“…and Thermovenabulum spp. [115]. It was noted that urolithin producers hosted at zero time a 33-fold greater population of Akkermansia muciniphila (phylum Actinobacteria) than the non-producers, and that after supplementation this differential was 47-fold [115], whereas Romo-Vaquero et al were able to associate urolithin A production with Gordonibacter [116], an organism not detected by Li et al These studies clearly demonstrate that there are two metabotypes with regard to ellagitannin catabolism -one for whom urolithin production is easily inducible and the other for which induction by dietary supplementation is more difficult or impossible, and that certain transformations can be achieved by more than one genus.…”

Food Additives and Contaminants: Effects on Human Gut Microbiota—A Review

“…Flavonols [57], quercetin [58,59], catechin and puerarin [59], anthocyanins [47], ellagitannins [60], resveratrol [61] and trans-resveratrol [58] are all reported to impact the activities of the GM. Quercetin supplementation resulted in an altered composition of the GM at different taxonomic levels, including the FBR and inhibiting the growth of bacterial species associated with diet-induced obesity, such as Erysipelotrichaceae, Bacillus spp., and Eubacterium cylindroides [58].…”

“…significantly. Li et al [60] demonstrated that ellagitannins can stimulate the growth of several bacterial genera with beneficial properties for human health, such as Akkermansia muciniphila, Butyrivibrio, Escherichia, Lactobacillus or Prevotella. Proanthocyanidins from grape seed can increase Lachnospiraceae, Clostridiales, Lactobacillus and Ruminococcacceae in female pigs [63].…”