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Updated: Sep 27, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Gut environment changes due to androgen deprivation therapy in patients with prostate cancer
Akimasa Kure1,2,3, Tomoya Tsukimi2,4, Chiharu Ishii2,4
1Department of Urology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
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.
Insights
Androgen deprivation therapy (ADT) for prostate cancer significantly alters gut microbiota diversity and composition, potentially increasing frailty and adverse outcomes. This study highlights the impact of ADT on the gut microbiome in cancer patients.
Area of Science:
- Oncology
- Microbiome Research
- Metabolomics
Background:
- Prostate cancer is projected to have over 1 million new cases by 2040.
- Androgen deprivation therapy (ADT) is a standard treatment for prostate cancer.
- The impact of ADT on gut microbiota and metabolome in prostate cancer patients is understudied.
Purpose of the Study:
- To investigate the relationship between testosterone levels and gut microbiota changes in Japanese prostate cancer patients undergoing ADT.
- To analyze the alterations in gut microbiome and metabolome profiles during ADT treatment.
Main Methods:
- A 24-week observational study involving 23 Japanese prostate cancer patients.
- Collection of sequential fecal and blood samples before and at multiple time points after ADT initiation.
- Bacterial 16S rRNA gene sequencing for microbiome analysis and capillary electrophoresis-time-of-flight mass spectrometry for metabolome analysis.
Main Results:
- Significant decrease in gut microbiota alpha- and beta-diversity at 24 weeks post-ADT.
- Significant changes in the relative abundance of Proteobacteria and specific metabolites including urea and lactate.
- Positive correlation observed between Proteobacteria abundance and lactate concentration, indicating dysbiosis.
Conclusions:
- ADT leads to detrimental changes in gut microbiota composition and diversity.
- These ADT-induced gut microbiome alterations may contribute to increased frailty and adverse outcomes in prostate cancer patients.
- Further research is warranted to explore therapeutic strategies targeting the gut microbiome in prostate cancer patients undergoing ADT.
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