title: Lignan transformation by gut bacteria lowers tumor burden in a gnotobiotic rat model of breast cancer.
abstract: High dietary lignan exposure is implicated in a reduced breast cancer risk in women. The bacterial transformation of plant lignans to enterolignans is thought to be essential for this effect. To provide evidence for this assumption, gnotobiotic rats were colonized with the lignan-converting bacteria Clostridium saccharogumia, Eggerthella lenta, Blautia producta and Lactonifactor longoviformis (LCC rats). Germ-free rats were used as the control. All animals were fed a lignan-rich flaxseed diet and breast cancer was induced with 7,12-dimethylbenz(a)anthracene. The lignan secoisolariciresinol diglucoside was converted into the enterolignans enterodiol and enterolactone in the LCC but not in the germ-free rats. This transformation did not influence cancer incidence at the end of the 13 weeks experimental period but significantly decreased tumor numbers per tumor-bearing rat, tumor size, tumor cell proliferation and increased tumor cell apoptosis in LCC rats. No differences between LCC and control rats were observed in the expression of the genes encoding the estrogen receptors (ERs) α, ERβ and G-coupled protein 30. The same was true for IGF-1 and EGFR involved in tumor growth. The activity of selected enzymes involved in the degradation of oxidants in plasma and liver was significantly increased in the LCC rats. However, plasma and liver concentrations of reduced glutathione and malondialdehyde, considered as oxidative stress markers, did not differ between the groups. In conclusion, our results show that the bacterial conversion of plant lignans to enterolignans beneficially influences their anticancer effects.
authors.affiliation: Department of Gastrointestinal Microbiology, German Institute of Human Nutrition Potsdam-Rehbruecke, D-14558 Nuthetal, Germany.
authors.forename: Hoda B
authors.initials: HB
authors.lastname: Mabrok
authors.forename: Robert
authors.initials: R
authors.lastname: Klopfleisch
authors.forename: Kadry Z
authors.initials: KZ
authors.lastname: Ghanem
authors.forename: Thomas
authors.initials: T
authors.lastname: Clavel
authors.forename: Michael
authors.initials: M
authors.lastname: Blaut
authors.forename: Gunnar
authors.initials: G
authors.lastname: Loh
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D001943:Breast Neoplasms / Q000517:prevention & control*; D002374:Catalase / Q000378:metabolism; D005232:Fatty Acids, Volatile / Q000032:analysis; D005260:Female; D005856:Germ-Free Life; D006304:Health Status; D007150:Immunohistochemistry; D007422:Intestines / Q000737:chemistry / Q000382:microbiology*; D017705:Lignans / Q000008:administration & dosage* / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D005232:Fatty Acids, Volatile; D017705:Lignans; D011960:Receptors, Estrogen; D002374:Catalase; D013482:Superoxide Dismutase