MP20-17 LARD DIET PROMOTES PROSTATE CANCER PROGRESSION THROUGH MODULATING GUT MICROBIOTA AND INTRATUMORAL LIPID METABOLISM

Abstract

You have accessJournal of UrologyCME1 Apr 2023MP20-17 LARD DIET PROMOTES PROSTATE CANCER PROGRESSION THROUGH MODULATING GUT MICROBIOTA AND INTRATUMORAL LIPID METABOLISM Hiromi Sato, Shintaro Narita, Yoshiko Takahashi, Masanori Ishida, Mizuki Kobayashi, Soki Kasima, Ryohei Yamamoto, Taketoshi Nara, Mingguo Huang, Kazuyuki Numakura, Mitsuru Saito, Toshiaki Yoshioka, and Tomonori Habuchi Hiromi SatoHiromi Sato More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Yoshiko TakahashiYoshiko Takahashi More articles by this author , Masanori IshidaMasanori Ishida More articles by this author , Mizuki KobayashiMizuki Kobayashi More articles by this author , Soki KasimaSoki Kasima More articles by this author , Ryohei YamamotoRyohei Yamamoto More articles by this author , Taketoshi NaraTaketoshi Nara More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Kazuyuki NumakuraKazuyuki Numakura More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Toshiaki YoshiokaToshiaki Yoshioka More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003245.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Lard diet (LD) is a risk factor for prostate cancer (PCa) progression. The role of dietary dysbiosis in the development of PCa is largely unknown, even though it has recently become clear that it plays a significant role in progression of many cancers. Herein, we performed a comprehensive gut microbiome and intratumoral mRNA omics analyses to analyze targetable molecules involved in LD-induced PCa progression via gut microbial alteration. METHODS: Pb-Cre; Pten (fl/fl) transgenic mice and C57BL6 mice subcutaneously inoculated with TRAMP-C2 PCa cells were fed with a LD rich in saturated fatty acid (SFA) or fish- oil diet (FOD) rich in polyunsaturated fatty acid. We obtained fecal and prostate/subcutaneous tumor samples. Using 16S rRNA gene amplicon sequencing, we compared the diversity and relative abundance of gut microbiota. We performed a cDNA microarray to assess the mRNA expression in the mouse PCa tissue. RESULTS: More weight and prostate/subcutaneous tumor volume were gained by the LD-fed mice in two mouse models compared to the FOD-fed mice. In an integrated analysis of the two models, the LD group and the FOD group formed different gut microbial clusters. According to microbiome analysis, order Lactobacillales was relatively more abundant in the FOD group than in the LD group, and order Clostridiales was enriched in the LD group compared to the FOD group. The proportion of order Lactbacillales in the gut was negatively associated with the body weight and prostate weight of the mice. In microarray analysis, we found the modulation of lipid metabolism and cholesterol biosynthesis pathways with 10 significantly modulated genes including sphingosine 1-phosphate receptor 2 (S1PR2) and low-density lipoprotein receptor (LDLR) in PCa tissues. Of these genes, S1PR2 was highly correlated with the abundance of order Lactobacillales in the mouse gut. Moreover, PCa patients with a higher Gleason score (≥8) and a higher body mass (BMI) index had significantly lower S1PR2 RNA levels in human prostatic specimens than those with a Gleason score ≤ 7 and lower BMI. CONCLUSIONS: SFA may accelerate PCa progression by altering particular gut microbial species and lipogenic genes in PCa. Therapeutics with alteration of gut microbiota and candidate genes involved in diet-induced PCa progression may be attractive in PCa. Source of Funding: GlaxoSmithKline plc © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e282 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hiromi Sato More articles by this author Shintaro Narita More articles by this author Yoshiko Takahashi More articles by this author Masanori Ishida More articles by this author Mizuki Kobayashi More articles by this author Soki Kasima More articles by this author Ryohei Yamamoto More articles by this author Taketoshi Nara More articles by this author Mingguo Huang More articles by this author Kazuyuki Numakura More articles by this author Mitsuru Saito More articles by this author Toshiaki Yoshioka More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement PDF downloadLoading ...