Akimasa Kure1,2,3, Tomoya Tsukimi2,4, Chiharu Ishii2,4, Wanping Aw2,4, Nozomu Obana3, Gaku Nakato5, Akiyoshi Hirayama2,4, Haruna Kawano1, Toshiyuki China1, Fumitaka Shimizu1, Masayoshi Nagata1, Shinji Isotani1, Satoru Muto1,6, Shigeo Horie7,8, Shinji Fukuda9,10,11,12. 1. Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. 2. Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan. 3. Transborder Medical Research Centre, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. 4. Systems Biology Programme, Graduate School of Media and Governance, Keio University, 5322 Endo, Fujisawa, Kanagawa, 252-0882, Japan. 5. Kanagawa Institute of Industrial Science and Technology, Life Science & Environment Research Centre (LiSE) 4th floor Room 4C-6, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-0821, Japan. 6. Department of Advanced Informatics for Genetic Diseases, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. 7. Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. shorie@juntendo.ac.jp. 8. Department of Advanced Informatics for Genetic Diseases, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. shorie@juntendo.ac.jp. 9. Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata, 997-0052, Japan. sfukuda@sfc.keio.ac.jp. 10. Transborder Medical Research Centre, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. sfukuda@sfc.keio.ac.jp. 11. Systems Biology Programme, Graduate School of Media and Governance, Keio University, 5322 Endo, Fujisawa, Kanagawa, 252-0882, Japan. sfukuda@sfc.keio.ac.jp. 12. Kanagawa Institute of Industrial Science and Technology, Life Science & Environment Research Centre (LiSE) 4th floor Room 4C-6, 3-25-13 Tonomachi, Kawasaki-ku, Kawasaki-shi, Kanagawa, 210-0821, Japan. sfukuda@sfc.keio.ac.jp.
Abstract
BACKGROUND: It is estimated that by 2040 there will be 1,017,712 new cases of prostate cancer worldwide. Androgen deprivation therapy (ADT) is widely used as a treatment option for all disease stages. ADT, and the resulting decline in androgen levels, may indirectly affect gut microbiota. Factors affecting gut microbiota are wide-ranging; however, literature is scarce on the effects of ADT on gut microbiota and metabolome profiles in patients with prostate cancer. METHODS: To study the changes of gut microbiome by ADT, this 24-week observational study investigated the relationship between testosterone levels and changes in gut microbiota in Japanese patients with prostate cancer undergoing ADT. Sequential faecal samples were collected 1 and 2 weeks before ADT, and 1, 4, 12, and 24 weeks after ADT. Blood samples were collected at almost the same times. Bacterial 16 S rRNA gene-based microbiome analyses and capillary electrophoresis-time-of-flight mass spectrometry-based metabolome analyses were performed. RESULTS: In total, 23 patients completed the study. The α- and ß-diversity of gut microbiota decreased significantly at 24 weeks after ADT (p = 0.017, p < 0.001, respectively). Relative abundances of Proteobacteria, Gammaproteobacteria, Pseudomonadales, Pseudomonas, and concentrations of urea, lactate, butyrate, 2-hydroxyisobutyrate and S-adenosylmethionine changed significantly after ADT (p < 0.05). There was a significant positive correlation between the abundance of Proteobacteria, a known indicator of dysbiosis, and the concentration of lactate (R = 0.49, p < 0.01). CONCLUSIONS: The decline in testosterone levels resulted in detrimental changes in gut microbiota. This dysbiosis may contribute to an increase in frailty and an increased risk of adverse outcomes in patients with prostate cancer.
BACKGROUND: It is estimated that by 2040 there will be 1,017,712 new cases of prostate cancer worldwide. Androgen deprivation therapy (ADT) is widely used as a treatment option for all disease stages. ADT, and the resulting decline in androgen levels, may indirectly affect gut microbiota. Factors affecting gut microbiota are wide-ranging; however, literature is scarce on the effects of ADT on gut microbiota and metabolome profiles in patients with prostate cancer. METHODS: To study the changes of gut microbiome by ADT, this 24-week observational study investigated the relationship between testosterone levels and changes in gut microbiota in Japanese patients with prostate cancer undergoing ADT. Sequential faecal samples were collected 1 and 2 weeks before ADT, and 1, 4, 12, and 24 weeks after ADT. Blood samples were collected at almost the same times. Bacterial 16 S rRNA gene-based microbiome analyses and capillary electrophoresis-time-of-flight mass spectrometry-based metabolome analyses were performed. RESULTS: In total, 23 patients completed the study. The α- and ß-diversity of gut microbiota decreased significantly at 24 weeks after ADT (p = 0.017, p < 0.001, respectively). Relative abundances of Proteobacteria, Gammaproteobacteria, Pseudomonadales, Pseudomonas, and concentrations of urea, lactate, butyrate, 2-hydroxyisobutyrate and S-adenosylmethionine changed significantly after ADT (p < 0.05). There was a significant positive correlation between the abundance of Proteobacteria, a known indicator of dysbiosis, and the concentration of lactate (R = 0.49, p < 0.01). CONCLUSIONS: The decline in testosterone levels resulted in detrimental changes in gut microbiota. This dysbiosis may contribute to an increase in frailty and an increased risk of adverse outcomes in patients with prostate cancer.
Authors: Lindsey A Torre; Freddie Bray; Rebecca L Siegel; Jacques Ferlay; Joannie Lortet-Tieulent; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2015-02-04 Impact factor: 508.702
Authors: Freddie Bray; Jacques Ferlay; Isabelle Soerjomataram; Rebecca L Siegel; Lindsey A Torre; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2018-09-12 Impact factor: 508.702
Authors: Leonid Yurkovetskiy; Michael Burrows; Aly A Khan; Laura Graham; Pavel Volchkov; Lev Becker; Dionysios Antonopoulos; Yoshinori Umesaki; Alexander V Chervonsky Journal: Immunity Date: 2013-08-22 Impact factor: 31.745
Authors: Gati K Panigrahi; Prakash P Praharaj; Hiroki Kittaka; Asit R Mridha; Olen M Black; Rakesh Singh; Roger Mercer; Adrie van Bokhoven; Kathleen C Torkko; Chapla Agarwal; Rajesh Agarwal; Zakaria Y Abd Elmageed; Hariom Yadav; Santosh K Mishra; Gagan Deep Journal: Cancer Med Date: 2019-01-08 Impact factor: 4.452
Authors: Nagi B Kumar; Stephanie Hogue; Julio Pow-Sang; Michael Poch; Brandon J Manley; Roger Li; Jasreman Dhillon; Alice Yu; Doratha A Byrd Journal: Cancers (Basel) Date: 2022-08-18 Impact factor: 6.575
Authors: Joseph Kai Man Li; Lynn Lin Wang; Becky Su Yan Lau; Ryan Tsz Hei Tse; Carol Ka Lo Cheng; Steven Chi Ho Leung; Christine Yim Ping Wong; Stephen Kwok Wing Tsui; Jeremy Yuen Chun Teoh; Peter Ka Fung Chiu; Chi Fai Ng Journal: Front Cell Infect Microbiol Date: 2022-08-16 Impact factor: 6.073