Presentation on theme: "Activation of pro-estrogens from hops by intestinal bacteria Sam Possemiers, Selin Bolca, Veerle Maervoet, Tom Van de Wiele, Arne Heyerick, Denis De Keukeleire."— Presentation transcript:
Activation of pro-estrogens from hops by intestinal bacteria Sam Possemiers, Selin Bolca, Veerle Maervoet, Tom Van de Wiele, Arne Heyerick, Denis De Keukeleire & Willy Verstraete Production of the phytoestrogen 8-prenylnaringenin Laboratory of Microbial Ecology & Technology (LabMET)
“Plant constituents which structurally or functionally mimic the female estrogen 17β- estradiol” Beneficial role in the prevention of osteoporosis, menopauzal complaints and cancers Applications! Phytoestrogens (1) 17β-estradiol
Phytoestrogens (2) 2 well known groups: Isoflavones from soy: daidzein, genistein Lignans from linseed, fruits, nuts… genistein Secoisolariciresinol (SECO)
Phytoestrogens (3) Common caracteristics: Crucial activation by the intestinal microbiota Daidzein equol SECO enterodiol, enterolacton Strong influence on biological activity! BUT: interindividual differences!!! E.g. only 1/3rd of population produces equol Beneficial effects depend on microbial community composition
Phytoestrogens from hop (1) Humulus lupulus L. (Hop) >Cannabaceae(+ Cannabis sativa L.) Mainly used in beer industry But also source of the prenylflavonoid 8- prenylnaringenin (8-PN) 3rd group of phytoestrogens
Phytoestrogens from hop (2) Research topic: Intestinal metabolism? Cfr other phytoestrogens: intestinal activation? Hop prenylflavonoids: 8-prenylnaringenin (8-PN): very low concentrations Isoxanthohumol (IX) and Xanthohumol (X): not estrogens but much higher concentrations. Metabolism of 8-PN, IX and X?
Isoxanthohumol acts as pro-estrogen (1) IX can be activated into 8-PN!
Isoxanthohumol acts as pro-estrogen (2) Desmethyl- xanthohumol + 6-Prenylnaringenin Xanthohumol (X) Isoxanthohumol (IX) Michael addition 8-Prenylnaringenin (8-PN) Michael addition Microbial O-demethylation OOH OH OH OH
Isoxanthohumol acts as pro-estrogen (3) IX can be activated into 8-PN! Relevance: 8-PN conc in beer are too low for biological effects Activation of IX: much higher exposure to 8-PN! BUT: interindividual differences Interindividual differences?
Interindividual differences in vitro (1) Experiment with 51 fecal samples Incubation immediately after defecation BHI + fecal samples (5%) 25 mg/L IX 37°C, anaerobic conditions HPLC and LC/MS analysis % high, moderate and slow 8-PN producers? Possemiers et al., Journal of Nutrition, July 2006
Interindividual differences in vivo (1) In vivo evaluation of the bioavailability and biotransformation of hop prenylflavonoids 5 day intervention study (5.5 mg IX/d) 50 postmenopauzal women urine collection: Absorption prenylflavonoids Detection and identification of metabolites Fecal sample collection In vitro IX into 8-PN conversion Molecular fingerprinting of intestinal community
In vivo (2): fecal samples High (A), moderate (C) and slow (B) IX-converter
In vivo (3): urine High (A), moderate (C) and slow (B) 8-PN excretion Good correlation between in vitro and in vivo!
Conclusions Intestinal transformation of hop flavonoids: Interindividual differences 1/3rd converted IX into hopein (8-PN) Good correlation in vitro and in vivo Intestinal bacteria are responsible for the conversion in vivo IX acts as pro-estrogen in food and supplements Up to 4 mg IX/L in beer and 5 mg/supplement Possible health effects not negligible! Exposure dependent on intestinal microbial community!
Contact information Posters: Possemiers et al. Bolca et al. LabMET – Ghent University Coupure Links 653 B-9000 Gent +32/9/