Eubacterium limosum activates isoxanthohumol from hops (Humulus lupulus L.) into the potent phytoestrogen 8-prenylnaringenin in vitro and in rat intestine.
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.
Laboratory of Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, B-9000 Gent, Belgium.
Sam
S
Possemiers
Sylvie
S
Rabot
Juan Carlos
JC
Espín
Aurélia
A
Bruneau
Catherine
C
Philippe
Antonio
A
González-Sarrías
Arne
A
Heyerick
Francisco A
FA
Tomás-Barberán
Denis
D
De Keukeleire
Willy
W
Verstraete
D000818:Animals; D001483:Base Sequence; D001711:Biotransformation; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D004032:Diet; D005051:Eubacterium / Q000235:genetics / Q000378:metabolism*; D005260:Female; D044950:Flavanones / Q000378:metabolism*; D005856:Germ-Free Life; D006801:Humans; D027582:Humulus / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008297:Male; D048789:Phytoestrogens / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D019936:Probiotics; D051381:Rats; D011916:Rats, Inbred F344; D044004:Xanthones / Q000378:metabolism*
C119737:8-prenylnaringenin; D017931:DNA Primers; D004269:DNA, Bacterial; D044950:Flavanones; D048789:Phytoestrogens; D044004:Xanthones; C512910:isoxanthohumol