Combined maternal and post-weaning high fat diet inhibits male offspring's prostate cancer tumorigenesis in transgenic adenocarcinoma of mouse prostate model.

Abstract

High fat diet (HFD) and its responsive change of gut microbiota are associated with numerous diseases in human and animal studies. But how maternal and post-weaning HFD may influence the tumorigenesis of prostate cancer (PCa) in male offspring has not yet been reported. We studied both solitary and combined effects of maternal or/and post-weaning HFD on the tumorigenesis of prostate in offspring using a transgenic adenocarcinoma of mouse prostate (TRAMP) model. TRAMP male mice (n = 24) were born to and fostered onto control diet or HFD-fed mothers, the weaned pups were further fed control or fat diet. All mice were sacrificed at the 28th week. The prostate histopathology was performed. The gut microbiota was analyzed by fecal 16S rRNA pyrosequencing, and the serum metabolites were determined by LC-MS/MS. Our results indicated that post-weaning HFD could significantly promote the PCa tumorigenesis in offspring (P = 0.031), and similar results were found in maternal HFD group but with no significant differences (P = 0.056). However, combined maternal and post-weaning HFD could significantly reduce the PCa tumorigenesis in offspring (P = 0.019). Significant differences in specific microbial populations and serum metabolites were observed across groups. For example, mice with combined maternal and post-weaning HFD had higher abundance of gut Lachonospiraceae, Roseburia, and Amycolatopsis, increased serum L-methionine (P = 0.0052), and decreased serum α-linolenic acid (P < 0.001). This study highlights the inhibitory effects of combined maternal and post-weaning HFD on PCa tumorigenesis, and provides new insights into the interactions between diet, gut microbiota, serum metabolites, and PCa.