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• W4226184423 abstract "You have accessJournal of UrologyCME1 May 2022PD46-09 LIPOPOLYSACCHARIDE FROM DYSBIOTIC GUT MICROBIOTA PROMOTES INFLAMMATORY PROSTATE CANCER GROWTH THROUGH HISTAMINE H1 RECEPTOR SIGNALING Makoto Matsushita, Kazutoshi Fujita, Takuji Hayashi, Hisako Kayama, Daisuke Motooka, Hiroaki Hase, Toshihiko Uemura, Akinaru Yamamoto, Gaku Yamamichi, Eisuke Tomiyama, Yoko Koh, Taigo Kato, Koji Hatano, Atsunari Kawashima, Motohide Uemura, Satoshi Nojima, Ryoichi Imamura, Kazutake Tsujikawa, Shota Nakamura, Kiyoshi Takeda, Eiichi Morii, and Norio Nonomura Makoto MatsushitaMakoto Matsushita More articles by this author , Kazutoshi FujitaKazutoshi Fujita More articles by this author , Takuji HayashiTakuji Hayashi More articles by this author , Hisako KayamaHisako Kayama More articles by this author , Daisuke MotookaDaisuke Motooka More articles by this author , Hiroaki HaseHiroaki Hase More articles by this author , Toshihiko UemuraToshihiko Uemura More articles by this author , Akinaru YamamotoAkinaru Yamamoto More articles by this author , Gaku YamamichiGaku Yamamichi More articles by this author , Eisuke TomiyamaEisuke Tomiyama More articles by this author , Yoko KohYoko Koh More articles by this author , Taigo KatoTaigo Kato More articles by this author , Koji HatanoKoji Hatano More articles by this author , Atsunari KawashimaAtsunari Kawashima More articles by this author , Motohide UemuraMotohide Uemura More articles by this author , Satoshi NojimaSatoshi Nojima More articles by this author , Ryoichi ImamuraRyoichi Imamura More articles by this author , Kazutake TsujikawaKazutake Tsujikawa More articles by this author , Shota NakamuraShota Nakamura More articles by this author , Kiyoshi TakedaKiyoshi Takeda More articles by this author , Eiichi MoriiEiichi Morii More articles by this author , and Norio NonomuraNorio Nonomura More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002614.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: High-fat diet (HFD) induce prostate inflammation and promote cancer growth. But the mechanism has not been entirely clear. We have reported that diet-influenced gut microbiota regulates prostate cancer (PCa) growth via IGF-1 signaling. In this study, we investigated the cause of HFD-induced inflammatory PCa growth and the role of gut microbiota in this process. METHODS: We compared between HFD-fed and control diet (CD)-fed prostate-specific Pten KO mice at 22 weeks of age as PCa models. HFD-fed mice were given histamine receptor antagonist. Tumor growth was evaluated by prostate weight and Ki67 staining. Gut microbiota compositions were analyzed by 16S rRNA gene sequencing of mouse feces. Histamine signaling in PCa was assessed at gene and protein level. RESULTS: HFD significantly increased prostate weight (0.25 vs. 0.46g, P = 0.01) and Ki67-positive cancer cell ratio (0.15 vs. 0.36, P = 0.01). cDNA microarray of PCa showed that expression of Hdc encoding histidine decarboxylase (HDC), which is responsible for histamine production, was upregulated in HFD-fed mice (Fold change = 2.71). The elevated expression of Hdc was also confirmed by quantitative PCR (P < 0.01). Infiltrating mast cells highly produced HDC protein, and mast cell counts around cancer foci were significantly increased in HFD-fed mice. Fexofenadine (Fexo), an H1 blocker, inhibited HFD-induced PCa growth, while ranitidine, an H2 blocker, had no inhibitory effect. Fexo reduced MDSC counts and suppressed IL6/STAT3 signaling in PCa of HFD-fed mice. In vitro, both histamine and Fexo did not affect the proliferation of DU145. HFD altered the composition of gut microbiota, and Shannon index suggesting diversity of gut microbiota was reduced in HFD-fed mice. Serum Lipopolysaccharide (LPS) levels were elevated in HFD-fed mice, and LPS injection resulted in upregulation of Hdc in PCa. CONCLUSIONS: We found that HFD caused gut microbiota dysbiosis and elevated systemic LPS level, which could promote inflammatory PCa progression through histamine H1 receptor signaling. These results suggest the existence of a new LPS and histamine-mediated “gut-prostate axis” in addition to the IGF-1-mediated axis. Source of Funding: This work was supported by research grants of The Japanese Urological Association © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e791 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Makoto Matsushita More articles by this author Kazutoshi Fujita More articles by this author Takuji Hayashi More articles by this author Hisako Kayama More articles by this author Daisuke Motooka More articles by this author Hiroaki Hase More articles by this author Toshihiko Uemura More articles by this author Akinaru Yamamoto More articles by this author Gaku Yamamichi More articles by this author Eisuke Tomiyama More articles by this author Yoko Koh More articles by this author Taigo Kato More articles by this author Koji Hatano More articles by this author Atsunari Kawashima More articles by this author Motohide Uemura More articles by this author Satoshi Nojima More articles by this author Ryoichi Imamura More articles by this author Kazutake Tsujikawa More articles by this author Shota Nakamura More articles by this author Kiyoshi Takeda More articles by this author Eiichi Morii More articles by this author Norio Nonomura More articles by this author Expand All Advertisement PDF DownloadLoading ..." @default.
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• W4226184423 title "PD46-09 LIPOPOLYSACCHARIDE FROM DYSBIOTIC GUT MICROBIOTA PROMOTES INFLAMMATORY PROSTATE CANCER GROWTH THROUGH HISTAMINE H1 RECEPTOR SIGNALING" @default.
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