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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Eubacterium limosum Activates Isoxanthohumol from Hops (Humulus lupulus L.) into the Potent Phytoestrogen 8-Prenylnaringenin In Vitro and in Rat Intestine^1–3,

⁴ Laboratory of Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, B-9000 Gent, Belgium; ⁵ INRA, UR 910, Ecology and Physiology of the Digestive Tract, F-78350 Jouy-en-Josas, France; ⁶ Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, ES-30100, Murcia, Spain; and ⁷ Laboratory of Pharmacognosy and Phytochemistry, Faculty of Pharmaceutical Sciences, Ghent University B-9000, Gent, Belgium

^* To whom correspondence should be addressed. E-mail: willy.verstraete{at}ugent.be.

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.