Gut environment changes due to androgen deprivation therapy in patients with prostate cancer

• Published in: Prostate cancer and prostatic diseases Vol. 26; no. 2; pp. 323 - 330
• Main Authors: Kure, Akimasa, Tsukimi, Tomoya, Ishii, Chiharu, Aw, Wanping, Obana, Nozomu, Nakato, Gaku, Hirayama, Akiyoshi, Kawano, Haruna, China, Toshiyuki, Shimizu, Fumitaka, Nagata, Masayoshi, Isotani, Shinji, Muto, Satoru, Horie, Shigeo, Fukuda, Shinji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2023; Nature Publishing Group
• Subjects: 45/23; 631/67; 692/308/53/2421; Abundance; Adenosylmethionine; Androgen Antagonists - adverse effects; Androgens; Biomedical and Life Sciences; Biomedicine; Cancer Research; Capillary electrophoresis; Deprivation; Digestive system; Dysbacteriosis; Dysbiosis - chemically induced; Electrophoresis; Endocrine therapy; Feces; Frailty; Humans; Intestinal microflora; Lactates; Lactic acid; Male; Mass spectrometry; Mass spectroscopy; Microbiomes; Microbiota; Microorganisms; Prostate cancer; Prostatic Neoplasms; Proteobacteria; Reproductive Medicine; rRNA; S-Adenosylmethionine; Side effects; Testosterone; Urea
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/s41391-022-00536-3

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.