Oestrogenicity of prenylflavonoids from hops: activation of pro-oestrogens by intestinal bacteria.

For many centuries, hops (Humulus lupulus L.) have been used as essential ingredient in beers, providing the typical bitterness and hoppy flavour. However, the last few years the plant has gained increasing attention as a source of prenylflavonoids and in 1999, 8-prenylnaringenin (8-PN) was identified as the most potent phyto-oestrogen known so far. Hop extracts are therefore now marketed to reduce menopausal complaints. However, 8-PN concentrations in hops are very low, and variable efficiency of these extracts was observed. Yet, hops also contain isoxanthohumol (IX) in much higher amounts (IX/8-PN ratio in hop extracts is typically 10-20). This article reviews our recent findings on how the human intestinal microbiota may activate IX. Depending on inter-individual differences in the intestinal transformation potential, this conversion could easily increase the 8-PN exposure 10-fold. The variability in efficacy of hop extracts may therefore be explained by variable intestinal metabolism. Based on this scientific knowledge, an innovative strategy was developed to decrease this variability. First, Eubacterium limosum, capable of rapidly metabolizing all IX into 8-PN, was isolated from the complex intestinal ecosystem. This bacterium was then used to develop a new generation of hop products with increased reliability in effect. This strategy involves the use of the bacterium as probiotic, in which the bacterium is administered in combination with the original hop extract. This leads to efficient intestinal 8-PN production, also in individuals who originally did not harbour the appropriate bacteria. The findings presented in this review can therefore be considered as a typical example that good insight in the specific metabolic potential of complex microbial communities and individual bacterial species may offer important opportunities for the management and modulation of the microbial organization towards a certain metabolic function.