TY - JOUR
T1 - Gut environment changes due to androgen deprivation therapy in patients with prostate cancer
AU - Kure, Akimasa
AU - Tsukimi, Tomoya
AU - Ishii, Chiharu
AU - Aw, Wanping
AU - Obana, Nozomu
AU - Nakato, Gaku
AU - Hirayama, Akiyoshi
AU - Kawano, Haruna
AU - China, Toshiyuki
AU - Shimizu, Fumitaka
AU - Nagata, Masayoshi
AU - Isotani, Shinji
AU - Muto, Satoru
AU - Horie, Shigeo
AU - Fukuda, Shinji
N1 - Funding Information:
We are grateful to the study participants. We would like to thank Yuka Ohara, Mitsuko Komatsu, Noriko Kagata, Noriko Fukuda, and Naoki Tanigawa for their technical support. Medical writing support, in accordance with GPP guidelines, was provided by Mediwrite Asia Inc Pte Ltd and included proofreading and editing services. This work was supported in part by JSPS KAKENHI (18H04805 to SF), AMED-CREST (JP20gm1010009 to SF), JST ERATO (JPMJER1902 to SF), the Takeda Science Foundation (to SF), the Food Science Institute Foundation (to SF), and the Programme for the Advancement of Research in Core Projects under Keio University’s Longevity Initiative (to SF).
Funding Information:
We are grateful to the study participants. We would like to thank Yuka Ohara, Mitsuko Komatsu, Noriko Kagata, Noriko Fukuda, and Naoki Tanigawa for their technical support. Medical writing support, in accordance with GPP guidelines, was provided by Mediwrite Asia Inc Pte Ltd and included proofreading and editing services. This work was supported in part by JSPS KAKENHI (18H04805 to SF), AMED-CREST (JP20gm1010009 to SF), JST ERATO (JPMJER1902 to SF), the Takeda Science Foundation (to SF), the Food Science Institute Foundation (to SF), and the Programme for the Advancement of Research in Core Projects under Keio University’s Longevity Initiative (to SF).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85128328647&partnerID=8YFLogxK
U2 - 10.1038/s41391-022-00536-3
DO - 10.1038/s41391-022-00536-3
M3 - Article
C2 - 35418210
AN - SCOPUS:85128328647
SN - 1365-7852
VL - 26
SP - 323
EP - 330
JO - Prostate Cancer and Prostatic Diseases
JF - Prostate Cancer and Prostatic Diseases
IS - 2
ER -
