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.
Highlights
The burden of urologic cancer is increasing globally because of population aging [1]
We reported that gut microbe B. pullicaecorum could regulate the Short-chain fatty acids (SCFAs) transporter and receptor to reduce colorectal cancer (CRC) progression [23]
We determined the protein level of different SCFArelated genes in mouse bladder urothelial cells after B. pullicaecorum administration, which increased the level of B. pullicaecorum in stools (Supplementary Materials Figure S2)
Summary
The burden of urologic cancer is increasing globally because of population aging [1]. In addition to prostate cancer, other urologic cancers such as bladder cancer and kidney cancer remain common malignancies worldwide [2] Among these urinary system tumors, urothelial carcinoma displays distinct histomorphological phenotypes [3,4] and is likely to arise from different uroprogenitor cells [5]. One SCFA, butyrate, synthesized from dietary carbohydrates by bacterial fermentation in the colon [15,19], may be a potent proliferation inhibitor of urothelial cancer of the bladder [15,20]. In this context, butyrate-induced growth inhibition is potentially clinically significant [20]. A better understanding of the role of butyrate-producing microbes and the correlation between butyrate and tumor suppressors in the development and progression of bladder cancer would be helpful for exploring new therapeutic options
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