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

SIMPLE SUMMARY: Prostate cancer (PCa) is still the most diagnosed cancer and the second cause of death among men worldwide. Studies have shown that the human microbiome and its metabolites such as short-chain fatty acids (SCFAs) play a key role in PCa development and progress, as well as response to anticancer treatments. Furthermore, studies have reported racial disparities in terms of microbiome composition and SCFA content across different human cancers, including colon, cervical, and colorectal cancer. Lastly, studies have shown that epigenetic modifications also play a crucial role in carcinogenesis and response to various treatment interventions. Therefore, more research is needed to fully understand underlying molecular mechanisms that lead to PCa in terms of the human microbiome, microbiome-derived metabolites, race, and epigenetic modifications. Importantly, this will advance efforts into personalized treatment strategies across various cancers, including PCa. 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.