BACKGROUND

Recent studies have highlighted the association between androgen deprivation therapy (ADT) and the gut microbiota in prostate cancer. However, the impact of long-term ADT remains to be explored.

METHODS

To examine changes in the gut microbial profile from short-term (a median of 7 months), and middle-term (a median of 18 months) to long-term ADT (>33 months), 16S rRNA data from 56 fecal samples were reanalyzed. Additionally, a two-sample Mendelian randomization was employed to investigate the relationships between particular microbial signatures and prostate cancer as well as testosterone levels.

RESULTS

In contrast to the short- and middle-term ADT groups, the long-term ADT group had significant changes in alpha and beta diversity. In particular, the relative abundance of genera such as Catenibacterium and Holdemanella decreased in the long-term ADT group, whereas the opportunistic bacterium (Erysipelatoclostridium) and Ruminococcus gnavus showed increased abundance over ADT time. Moreover, a two-sample Mendelian randomization analysis revealed the negative associations between genetically predicated genera Coprobacter, Ruminococcaceae UCG002/011, and Defluviitaleacea-UCG-011, and testosterone levels.

CONCLUSIONS

In conclusion, long-term ADT use in prostate cancer patients was associated with detrimental changes in gut microbiota, including an increase in genera related to testosterone synthesis and opportunistic bacteria. These changes may be related to disease progression and side effects of long-term ADT while further longitudinal studies are required to prove this relationship.