Yang HJ, et al. Investig Clin Urol. 2023 Jan;64(1):3-12. https://doi.org/10.4111/icu.20220370

Our knowledge that “urine is sterile” is no longer accepted after the development of a next-generation sequencing (NGS) test. Using NGS, microbiota in the human body were discovered, and it is expected that this will improve our understanding of human diseases. However, the mechanism involved in the effect of the microbiome on diseases is still poorly understood. Associations of gut microbiome with diseases have been recently reported. Based on such associations, bladder–gut–brain axis, gut–bladder axis, gut–vagina–bladder axis, and gut–kidney axis as novel mechanisms of action of the microbiome have been suggested. Each axis can influence the development and progression of disease through interactions. In these interactions, metabolites of the microbiome including short-chain fatty acids (SCFA) and the inflammasome play an important role. Inflammasomes are multiprotein oligomers that can initiate inflammatory responses. Inflammasomes can trigger inflammation and pyroptosis and ultimately contribute to disease development. SCFAs play an important role in immune cell migration, cytokine production, and maintenance of cellular homeostasis. Associations of inflammasomes with systemic diseases such as obesity and insulin resistance have been reported. The roles of inflammasomes and SCFAs in kidney, bladder, and prostate diseases have also been revealed recently.

Yoo JJ, et al. Investig Clin Urol. 2024 Jul;65(4):378-390. https://doi.org/10.4111/icu.20230369

A promising de novo approach for the treatment of Castration-resistant prostate cancer (CRPC) exploits cell-mediated enzyme prodrug therapy comprising cytosine deaminase (CD) and fluorouracil (5-FC). The aim of this study was to determine the potential of bacterial CD-overexpressing hTERT-immortalized human adipose stem cells (hTERT-ADSC.CD) to suppress CRPC. A lentiviral vector encoding a bacterial CD gene was used to transfect and to generate the hTERT-ADSC.CD line. The ability of the cells to migrate selectively towards malignant cells was investigated in vitro. PC3 and hTERT-ADSC.CD cells were co-cultured. hTERT-ADSC.CD and 1 × 10⁶ PC3 cells were administered to nude mice via intracardiac and subcutaneous injections, respectively, and 5-FC was given for 14 days. hTERT-ADSC.CD were successfully engineered. Enhanced in vitro hTERT-ADSC.CD cytotoxicity and suicide effect were evident following administration of 5 μM 5-FC. hTERT-ADSC.CD, together with 5-FC, augmented the numbers of PC3 cells undergoing apoptosis. In comparison to controls administered hTERT-ADSC.CD monotherapy, hTERT-ADSC.CD in combination with 5-FC demonstrated a greater suppressive effect on tumor. In CPRC-bearing mice, tumor suppression was enhanced by the combination of CD-overexpressing ADSC and the prodrug 5-FC. Stem cells exhibiting CD gene expression are a potential novel approach to treatment for CRPC.