Supplementation of Probiotic Butyricicoccus pullicaecorum Mediates Anticancer Effect on Bladder Urothelial Cells by Regulating Butyrate-Responsive Molecular Signatures

Yen-Chieh Wang 1 2Wei-Chi Ku 2Chih-Yi Liu 2 3Yu-Che Cheng 2 4 5Chih-Cheng Chien 2 6Kang-Wei Chang 7 8Chi-Jung Huang 4 9

Affiliations
  1. Department of Urology, Cathay General Hospital, Taipei 106438, Taiwan.
  2. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242062, Taiwan.
  3. Department of Pathology, Sijhih Cathay General Hospital, New Taipei 221037, Taiwan.
  4. Department of Medical Research, Cathay General Hospital, Taipei 106438, Taiwan.
  5. Department of Biomedical Sciences and Engineering, National Central University, Taoyuan 320317, Taiwan.
  6. Department of Anesthesiology, Cathay General Hospital, Taipei 106438, Taiwan.
  7. Taipei Neuroscience Institute, Taipei Medical University, Taipei 110301, Taiwan.
  8. Laboratory Animal Center, Taipei Medical University, Taipei 110301, Taiwan.
  9. Department of Biochemistry, National Defense Medical Center, Taipei 114201, Taiwan.

ABSTRACT

In bladder cancer, urothelial carcinoma is the most common histologic subtype, accounting for more than 90% of cases. Pathogenic effects due to the dysbiosis of gut microbiota are localized not only in the colon, but also in regulating bladder cancer distally. Butyrate, a short-chain fatty acid produced by gut microbial metabolism, is mainly studied in colon diseases. Therefore, the resolution of the anti-cancer effects of butyrate-producing microbes on bladder urothelial cells and knowledge of the butyrate-responsive molecules must have clinical significance. Here, we demonstrate a correlation between urothelial cancer of the bladder and Butyricicoccus pullicaecorum. This butyrate-producing microbe or their metabolite, butyrate, mediated anti-cancer effects on bladder urothelial cells by regulating cell cycle, cell growth, apoptosis, and gene expression. For example, a tumor suppressor against urothelial cancer of the bladder, bladder cancer-associated protein, was induced in butyrate-treated HT1376 cells, a human urinary bladder cancer cell line. In conclusion, urothelial cancer of the bladder is a significant health problem. To improve the health of bladder urothelial cells, supplementation of B. pullicaecorum may be necessary and can further regulate butyrate-responsive molecular signatures.

Keywords: Butyricicoccus pullicaecorum; apoptosis; bladder cancer-associated protein; butyrate; urothelial bladder cancer.

>Diagnostics (Basel). 2021 Dec 4;11(12):2270. doi: 10.3390/diagnostics11122270.