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

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.

Butyrate supplementation regulates expression of chromosome segregation 1‑like protein to reverse the genetic distortion caused by p53 mutations in colorectal cancer

“…In particular, patients with inflammatory bowel disease or CRC were found to have lower concentrations of the butyrate-producing microbe butyricicoccus pullicaecorum in their stools ( 10 , 26 ). In addition, the culture supernatant of B. pullicaecorum is rich in butyrates and can strengthen intestinal barrier function ( 17 , 26 ), which supports the pharmabiotic potential B. pullicaecorum for clinical application ( 10 , 20 , 27 , 28 ). However, the possible association between CSE1L and/or the butyrate-producing B. pullicaecorum in the development of CRC remain poorly understood.…”

“…However, the effects of butyrate in CRC and the molecular mechanism underlying such effects remain unclear ( 19 ). Butyrate has been previously documented to downregulate the expression of a number of genes, including placenta specific 8 protein, toll-like receptor 4 and glucose 6-phosphatase ( 10 , 20 – 22 ). It can attenuate the lipopolysaccharide-induced inflammation of intestinal epithelial cells whilst exerting antioncogenic potential in LS1034 or WiDr human CRC cells by promoting p53 gene expression ( 23 – 25 ).…”

Bladder cancer-associated microbiota: Recent advances and future perspectives

“…Butyrate mediates antitumor effects on bladder uroepithelial cells via two short-chain fatty acid G protein-coupled receptors, GPR43 and GPR109B. However, the limitation of this study was that the findings were only validated in BC cell lines and mouse models [ 91 ]. Meanwhile, He et al also observed changes in butyrate levels while evaluating the effect of the gut microbiota in BC.…”

Anticancer Effects of Gut Microbiota-Derived Short-Chain Fatty Acids in Cancers

“…BA is typically diagnosed in older people and is caused by immune dysregulation-related tumorigenicity induced by age-associated metabolic alterations in the bladder microbiome [ 70 ]. The administration of B. pullicaecorum to mice increased SCFA-related gene expression in mouse bladder urothelial cells, and an in vitro analysis showed that treatment with NaB induced apoptosis via an increase in FasL protein levels in the HT1376 bladder cancer cell line [ 71 ]. In addition, in T24 and 5637 bladder cancer cell lines, NaB treatment induced apoptosis and reduced the cell migration rate.…”