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

Abstract

Background 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. Methods 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. Results 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). Conclusions 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.

Methyl-Donor Micronutrient for Gestating Sows: Effects on Gut Microbiota and Metabolome in Offspring Piglets

“…For hydrophilic interaction liquid chromatography (HILIC) separation, samples were analyzed using a 2.1 × 100 mm ACQUIY UPLC BEH Amide 1.7 μm column (Waters, Ireland). Chromatographic conditions and Q-TOF mass spectrometry conditions were as outlined by Liu et al ( 19 ), electrospray ionization (ESI) positive mode was used for detection.…”

Gut microbiota-derived short-chain fatty acids promote prostate cancer progression via inducing cancer cell autophagy and M2 macrophage polarization

“…High-quality reads were aligned using FLASH, and operational taxonomic units (OTUs) was delineated using UCLUST at 97% cutoff. LEfSe analysis was used to detect differential microbiotas [21] .…”

Maternal obesity and the impact of associated early-life inflammation on long-term health of offspring

“…On the contrary, exposure to maternal obesity during early life may directly reprogram tissues of different organ systems such that they are more likely to undergo tumorigenesis. Animal studies also suggest that maternal obesity increases the risk of hepatocellular carcinoma (Sun et al, 2020), mammary cancer (La Merrill et al, 2010;, prostate cancer (Benesh et al, 2013;Yang et al, 2018;Liu et al, 2019) and lung cancer (Shi et al, 2021) and some of these increased risks are attributed to the reprogrammed immune cells in the tumor microenvironment. However, clinical significance of the data is understudied and needs further elucidation.…”