Activation of Proestrogens from Hops (Humulus lupulus L.) by Intestinal Microbiota; Conversion of Isoxanthohumol into 8-Prenylnaringenin

Abstract

Hop, an essential ingredient in most beers, contains a number of prenylflavonoids, among which 8-prenylnaringenin (8-PN) would be the most potent phytoestrogen currently known. Although a number of health effects are attributed to these compounds, only a few reports are available about the bioavailability of prenylflavonoids and the transformation potency of the intestinal microbial community. To test these transformations, four fecal samples were incubated with xanthohumol, isoxanthohumol (IX), and 8-PN. Upon incubation with IX, present in strong ales up to 4 mg/L, 36% was converted into 8-PN in one fecal sample and the estrogenic properties of the sample drastically increased. In an experiment with 12 fecal cultures, this conversion was observed in one-third of the samples, indicating the importance of interindividual variability in the intestinal microbial community. Eubacterium limosum was identified to be capable of this conversion (O-demethylation) of IX into 8-PN, and after strain selection, a conversion efficiency of 90% was achieved. Finally, strain supplementation to a nonconverting fecal sample led to rapid and high 8-PN production at only 1% (v/v) addition. Up to now, the concentration of 8-PN in beer was considered too low to affect human health. However, these results show that the activity of the intestinal microbial community could more than 10-fold increase the exposure concentration. Because prenylflavonoids are present in many beers with IX being the major constituent, the results raise the question whether moderate beer consumption might contribute to increased in vivo levels of 8-PN and even influence human health.

The content of hop prenylflavonoids in czech and foreign beers.

“…Bylo však zjiš-těno, že bakterie střevního traktu jsou schopny transformovat isoxanthohumol pří-tomný v pivu na 8-PN. Denní příjem fytoestrogenu pravidelnou konzumací piva tak může stoupnout až na fyziologicky aktivní hladinu [11,12].…”

“…However, it was found that microorganisms in the intestinal tract are able to transform the isoxanthohumol present in beer to 8-PN. By regular consumption of beer the daily intake of phytoestrogen can reach an active physiological level [11,12].…”

Interindividual differences in phytochemical metabolism and disposition

“…Isoxanthohumol, produced from the hop-derived prenylchalcone xanthohumol during the beermaking process, is the principal prenylflavonoid present in beer at concentrations ranging from 0.5 mg/L up to 4 mg/L [41]. It is metabolized by gut bacteria to 8-prenylnaringenin (8-PN), one of the most potent phytoestrogens currently known.…”

A Review of the Medicinal Uses and Pharmacology of Ashitaba

“…In a study conducted on human microbiota-associated rats, the overall excretion of xanthohumol and its related metabolites after two days was only 4.2 % of the ingested amount, indicating that this compound is likely hydrolyzed by human intestinal microorganisms [43]. Additionally, interindividual variability in gut microbiota was found to play a large role in the availability of xanthohumol, and some species of bacteria rapidly hydrolyze this chalcone into 8-prenylnaringenin, a potent phytoestrogen that can affect estrogen signaling pathways [42][43][44]. The associated health effects of the consumption of xanthohumol depends largely on the amount ingested as well as on the phenotype of the individual ingesting this compound.…”