Akkermansia muciniphila Metabolite Inosine Inhibits Castration Resistance in Prostate Cancer

被引:0
作者
Yu, Yao [1 ]
Li, Leqian [1 ]
Yang, Qishen [1 ]
Xue, Jingwen [1 ]
Wang, Benlin [1 ]
Xie, Ming [1 ]
Shangguan, Wentai [1 ]
Zhu, Zhangrui [1 ]
Wu, Peng [1 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Urol, Guangzhou 510515, Peoples R China
基金
中国国家自然科学基金;
关键词
castration-resistant prostate cancer; gut microbiota; androgen deprivation therapy; Akkermansia muciniphila; inosine; ANTIGEN; NADIR; MICROBIOME; PREDICTS; SURVIVAL; TIME;
D O I
10.3390/microorganisms12081653
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Prostate cancer (PCa) is initially sensitive to androgen deprivation therapy (ADT) but ultimately develops resistance and progresses to castration-resistant prostate cancer (CRPC) with a poor prognosis. This study indicated that some PCa patients and mice were more sensitive to ADT and entered CRPC later, which was related to the gut microbiota, especially the enrichment of Akkermansia muciniphila (AKK). Untargeted metabolomics analysis found that serum inosine level was upregulated in the treatment-sensitive group and significantly correlated with AKK. Furthermore, we revealed that intestinal permeability and serum lipopolysaccharide (LPS) levels increased in treatment-resistant mice. LPS stimulated the upregulation of p-NF-kappa B p65 and AR in tumors. Supplementing AKK metabolite inosine could alleviate intestinal barrier damage and reduce serum LPS level, ultimately inhibiting castration resistance via the LPS/NF-kappa B/AR axis. Finally, we constructed a predictive model for CRPC combining gut microbiota and clinical information (AUC = 0.729). This study revealed the potential mechanism of gut microbiota on CRPC and provided potential therapeutic targets and prognostic indicators.
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页数:18
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共 57 条
  • [1] AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer
    Antonarakis, Emmanuel S.
    Lu, Changxue
    Wang, Hao
    Luber, Brandon
    Nakazawa, Mary
    Roeser, Jeffrey C.
    Chen, Yan
    Mohammad, Tabrez A.
    Chen, Yidong
    Fedor, Helen L.
    Lotan, Tamara L.
    Zheng, Qizhi
    De Marzo, Angelo M.
    Isaacs, John T.
    Isaacs, William B.
    Nadal, Rosa
    Paller, Channing J.
    Denmeade, Samuel R.
    Carducci, Michael A.
    Eisenberger, Mario A.
    Luo, Jun
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (11) : 1028 - 1038
  • [2] Akkermansia muciniphila phospholipid induces homeostatic immune responses
    Bae, Munhyung
    Cassilly, Chelsi D.
    Liu, Xiaoxi
    Park, Sung-Moo
    Tusi, Betsabeh Khoramian
    Chen, Xiangjun
    Kwon, Jaeyoung
    Filipcik, Pavel
    Bolze, Andrew S.
    Liu, Zehua
    Vlamakis, Hera
    Graham, Daniel B.
    Buhrlage, Sara J.
    Xavier, Ramnik J.
    Clardy, Jon
    [J]. NATURE, 2022, 608 (7921) : 168 - +
  • [3] Glucocorticoids and Androgens Protect From Gastric Metaplasia by Suppressing Group 2 Innate Lymphoid Cell Activation
    Busada, Jonathan T.
    Peterson, Kylie N.
    Khadka, Stuti
    Xu, Xiaojiang
    Oakley, Robert H.
    Cook, Donald N.
    Cidlowski, John A.
    [J]. GASTROENTEROLOGY, 2021, 161 (02) : 637 - +
  • [4] Current therapy and drug resistance in metastatic castration-resistant prostate cancer
    Cai, Maoping
    Song, Xian-Lu
    Li, Xin-An
    Chen, Mingkun
    Guo, Jiading
    Yang, Dong Hua
    Chen, Zhanghui
    Zhao, Shan-Chao
    [J]. DRUG RESISTANCE UPDATES, 2023, 68
  • [5] Cani PD, 2022, NAT REV GASTRO HEPAT, V19, P625, DOI 10.1038/s41575-022-00631-9
  • [6] QIIME allows analysis of high-throughput community sequencing data
    Caporaso, J. Gregory
    Kuczynski, Justin
    Stombaugh, Jesse
    Bittinger, Kyle
    Bushman, Frederic D.
    Costello, Elizabeth K.
    Fierer, Noah
    Pena, Antonio Gonzalez
    Goodrich, Julia K.
    Gordon, Jeffrey I.
    Huttley, Gavin A.
    Kelley, Scott T.
    Knights, Dan
    Koenig, Jeremy E.
    Ley, Ruth E.
    Lozupone, Catherine A.
    McDonald, Daniel
    Muegge, Brian D.
    Pirrung, Meg
    Reeder, Jens
    Sevinsky, Joel R.
    Tumbaugh, Peter J.
    Walters, William A.
    Widmann, Jeremy
    Yatsunenko, Tanya
    Zaneveld, Jesse
    Knight, Rob
    [J]. NATURE METHODS, 2010, 7 (05) : 335 - 336
  • [7] ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer
    Cato, Laura
    de Tribolet-Hardy, Jonas
    Lee, Irene
    Rottenberg, Jaice T.
    Coleman, Ilsa
    Melchers, Diana
    Houtman, Rene
    Xiao, Tengfei
    Li, Wei
    Uo, Takuma
    Sun, Shihua
    Kuznik, Nane C.
    Goeppert, Bettina
    Ozgun, Fatma
    van Royen, Martin E.
    Houtsmuller, Adriaan B.
    Vadhi, Raga
    Rao, Prakash K.
    Li, Lewyn
    Balk, Steven P.
    Den, Robert B.
    Trock, Bruce J.
    Karnes, R. Jeffrey
    Jenkins, Robert B.
    Klein, Eric A.
    Davicioni, Elai
    Gruhl, Friederike J.
    Long, Henry W.
    Liu, X. Shirley
    Cato, Andrew C. B.
    Lack, Nathan A.
    Nelson, Peter S.
    Plymate, Stephen R.
    Groner, Anna C.
    Brown, Myles
    [J]. CANCER CELL, 2019, 35 (03) : 401 - +
  • [8] Time to Prostate-Specific Antigen Nadir Independently Predicts Overall Survival in Patients Who Have Metastatic Hormone-Sensitive Prostate Cancer Treated With Androgen-Deprivation Therapy
    Choueiri, Toni K.
    Xie, Wanling
    D'Amico, Anthony V.
    Ross, Robert W.
    Hu, Jim C.
    Pomerantz, Mark
    Taplin, Mary-Ellen
    Kantoff, Philip W.
    Sartor, Oliver
    Oh, William K.
    [J]. CANCER, 2009, 115 (05) : 981 - 987
  • [9] Deep, rapid, and durable prostate-specific antigen decline with apalutamide plus androgen deprivation therapy is associated with longer survival and improved clinical outcomes in TITAN patients with metastatic castration-sensitive prostate cancer
    Chowdhury, S.
    Bjartell, A.
    Agarwal, N.
    Chung, B. H.
    Given, R. W.
    Gomes, A. J. Pereira de Santana
    Merseburger, A. S.
    Ozguroglu, M.
    Soto, A. Juarez
    Uemura, H.
    Ye, D.
    Brookman-May, S. D.
    Londhe, A.
    Bhaumik, A.
    Mundle, S. D.
    Larsen, J. S.
    McCarthy, S. A.
    Chi, K. N.
    [J]. ANNALS OF ONCOLOGY, 2023, 34 (05) : 477 - 485
  • [10] Gut microbiome responds to alteration in female sex hormone status and exacerbates metabolic dysfunction
    Cross, Tzu-Wen L.
    Simpson, Abigayle M. R.
    Lin, Ching-Yen
    Hottmann, Natasha M.
    Bhatt, Aadra P.
    Pellock, Samuel J.
    Nelson, Erik R.
    Loman, Brett R.
    Wallig, Matthew A.
    Vivas, Eugenio I.
    Suchodolski, Jan
    Redinbo, Matthew R.
    Rey, Federico E.
    Swanson, Kelly S.
    [J]. GUT MICROBES, 2024, 16 (01)