Eubacterium limosum activates isoxanthohumol from hops (Humulus lupulus L.) into the potent phytoestrogen 8-prenylnaringenin in vitro and in rat intestine

J Nutr. 2008 Jul;138(7):1310-6. doi: 10.1093/jn/138.7.1310.

Abstract

Recently, it was shown that the exposure to the potent hop phytoestrogen 8-prenylnaringenin (8-PN) depends on intestinal bacterial activation of isoxanthohumol (IX), but this occurs in only one-third of tested individuals. As the butyrate-producing Eubacterium limosum can produce 8-PN from IX, a probiotic strategy was applied to investigate whether 8-PN production could be increased in low 8-PN producers, thus balancing phytoestrogen exposure. Using fecal samples from high (Hop +) and low (Hop -) 8-PN-producing individuals, a Hop + and Hop - dynamic intestinal model was developed. In parallel, Hop + and Hop - human microbiota-associated rats were developed, germ-free (GF) rats acting as negative controls. IX and then IX + E. limosum were administered in the intestinal model and to the rats, and changes in 8-PN production and exposure were assessed. After dosing IX, 80% was converted into 8-PN in the Hop + model and highest 8-PN production, plasma concentrations, and urinary and fecal excretion occurred in the Hop + rats. Administration of the bacterium triggered 8-PN production in the GF rats and increased 8-PN production in the Hop - model and Hop - rats. 8-PN excretion was similar in the feces (294.1 +/- 132.2 nmol/d) and urine (8.5 +/- 1.1 nmol/d ) of all rats (n = 18). In addition, butyrate production increased in all rats. In conclusion, intestinal microbiota determined 8-PN production and exposure after IX intake. Moreover, E. limosum administration increased 8-PN production in low producers, resulting in similar 8-PN production in all rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Biotransformation
  • DNA Primers / genetics
  • DNA, Bacterial / genetics
  • DNA, Bacterial / isolation & purification
  • Diet
  • Eubacterium / genetics
  • Eubacterium / metabolism*
  • Female
  • Flavanones / metabolism*
  • Germ-Free Life
  • Humans
  • Humulus / metabolism*
  • In Vitro Techniques
  • Intestinal Mucosa / metabolism
  • Intestines / microbiology
  • Male
  • Phytoestrogens / metabolism*
  • Polymerase Chain Reaction
  • Probiotics
  • Rats
  • Rats, Inbred F344
  • Xanthones / metabolism*

Substances

  • 8-prenylnaringenin
  • DNA Primers
  • DNA, Bacterial
  • Flavanones
  • Phytoestrogens
  • Xanthones
  • isoxanthohumol