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.
