High dietary fat intake lowers serum equol concentration and promotes prostate carcinogenesis in a transgenic mouse prostate model.

Consumption of diet high in soy products is suggested to contribute to lower prostate cancer incidence in Asian men. But little has been known about the influences of dietary patterns on gut microbiota and microbiota-mediated isoflavone metabolism. Here, we determined the influences of western pattern diet on prostate carcinogenesis, gut microbiota and microbiota-mediated equol metabolism using a transgenic adenocarcinoma of mouse prostate (TRAMP) model. We mimicked the western pattern diet using a high fat diet (HFD). TRAMP mice were fed with either control diet (CD) or HFD. At the age of 24 weeks, mice were orally administered daidzein over a 4-day period, and then sacrificed. The serum daidzein and equol were analyzed by ultra high performance liquid chromatography. Fecal microbiome was analyzed with fecal 16S rRNA pyrosequencing, and prostate was dissected and performed with histopathology. HFD could promote prostate carcinogenesis in TRAMP mice (p = 0.045). The daidzein showed no significant differences between CD and HFD groups, while equol was significantly decreased in HFD group (p = 0.019). Fecal microbiotas differed between the two groups, 21 microbial phylotypes were increased and 11 phylotypes were decreased in abundance in HFD group, including decreased abundance of equol-producing bacterium Adlercreutzia (0.08% vs. 0.27%). HFD may promote prostate carcinogenesis through adversely affecting equol-producing bacterium. Further functional validations are required to ascertain the mechanism of those HFD-responsive bacteria in carcinogenesis.