PRODUCTION OF PHYTOESTROGENS FROM HOPS BY INTESTINAL BACTERIA: FROM DISCOVERY TO PRODUCT DEVELOPMENT

Abstract

For many centuries, hops (Humulus lupulus L.) have been used as essential ingredient in beer, providing the typical bitterness and hoppy flavor. However, in the last few years the plant has gained increasing attention as a source of prenylflavonoids and in 1999, 8-prenylnarigenin (8-PN) was identified as the most potent phytoestrogen 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 manuscript will review our recent findings that human intestinal microbiota may activate isoxanthohumol (IX). Depending on inter-individual differences in the intestinal transformation potential, this conversion could easily increase the 8-PN exposure tenfold. 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 reduce 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 reduced variability 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 harbor the appropriate bacteria.