Dissecting Microbiome-Derived SCFAs in Prostate Cancer: Analyzing Gut Microbiota, Racial Disparities, and Epigenetic Mechanisms

Abstract

Prostate cancer (PCa) continues to be the most diagnosed cancer and the second primary cause of fatalities in men globally. There is an abundance of scientific evidence suggesting that the human microbiome, together with its metabolites, plays a crucial role in carcinogenesis and has a significant impact on the efficacy of anticancer interventions in solid and hematological cancers. These anticancer interventions include chemotherapy, immune checkpoint inhibitors, and targeted therapies. Furthermore, the microbiome can influence systemic and local immune responses using numerous metabolites such as short-chain fatty acids (SCFAs). Despite the lack of scientific data in terms of the role of SCFAs in PCa pathogenesis, recent studies show that SCFAs have a profound impact on PCa progression. Several studies have reported racial/ethnic disparities in terms of bacterial content in the gut microbiome and SCFA composition. These studies explored microbiome and SCFA racial/ethnic disparities in cancers such as colorectal, colon, cervical, breast, and endometrial cancer. Notably, there are currently no published studies exploring microbiome/SCFA composition racial disparities and their role in PCa carcinogenesis. This review discusses the potential role of the microbiome in PCa development and progression. The involvement of microbiome-derived SCFAs in facilitating PCa carcinogenesis and their effect on PCa therapeutic response, particularly immunotherapy, are discussed. Racial/ethnic differences in microbiome composition and SCFA content in various cancers are also discussed. Lastly, the effects of SCFAs on PCa progression via epigenetic modifications is also discussed.

Revealing the Urinary Microbiota in Prostate Cancer: A Comprehensive Review Unveiling Insights into Pathogenesis and Clinical Application

“…Although the urinary microbiota in prostate cancer pathogenesis is still being actively researched, its contribution to our understanding of how bacterial communities interact with this relatively common malignancy can be quite revealing (33).…”

Role of the gut microbiota in tumorigenesis and treatment

“…Diet and physical activity also play important roles in the development and progression of PCa, particularly in relation to ethnicity, at different incidence rates 105 . Additionally, an increasing body of research over the past decade has demonstrated the significant role that the gut microbiota plays in the occurrence and development of PCa 106 , 107 . Liss et al conducted an analysis of the gut microbiota in 133 U.S. men who underwent prostate biopsy; they performed 16S rRNA amplicon sequencing on 105 samples (64 with cancer and 41 without cancer) 108 .…”