Gut microbiota dysbiosis is related to cancer development and progression. Our previous study showed that Ruminococcus was more abundant in CRPC (Castration-resistant prostate cancer) than HSPC (Hormone-sensitive prostate cancer) individuals. Here, we determined the potential mechanism of microbiota dysbiosis in prostate cancer (PCa) progression. Metagenomics was used to verify the gut microbial discrepancies between CRPC and HSPC individuals. Fecal microbiota transplantation (FMT) was performed by transferring the fecal suspension of CRPC or HSPC individuals to TRAMP mice. Afterwards, the mice’s prostate histopathology and gut microbiota composition were determined. Since Ruminococcus was demonstrated to correlate with phospholipid metabolism, we used lipidomics to examine the mice’s fecal lipid profiles. The expression of LPCAT1 the key enzyme for phospholipid remodeling in mice prostate was also examined. Meanwhile, both microbial functions prediction and LPCAT1 GSEA analysis (Gene Set Enrichment Analysis) indicated DNA repair pathways, we further determined the expressions of RAD51 and DNA-PKcs in mice prostate. The results showed that gut Ruminococcus was significantly more abundant in CRPC individuals. FMT using CRPC feces accelerated mice’s PCa progression and increased their gut Ruminococcus abundance. Majority of fecal lipids including lysophosphatidylcholine and phosphatidylcholine were upregulated in CRPC FMT treated mice, accompanied with enhanced expressions of LPCAT1, RAD51, and DNA-PKcs in mice prostate. We reported an abundant colonization of Ruminococcus in the gut of CRPC individuals and mice receiving their fecal suspensions, and revealed the promotive capability of Ruminococcus in PCa progression via upregulating LPCAT1 and DNA repair protein expressions. The bacterium and its downstream pathways may become the targets of therapies for PCa in the future.

Background: It is known that gut microbiota can regulate cancer therapies. We hypothesized that gut microbiota may interact with androgen deprivation therapy (ADT) in the process of castration-resistant prostate cancer (CRPC). Here, the differences in gut microbiota between matched hormone-sensitive prostate cancer (HSPC) and CRPC were determined before and after ADT. Methods: We profiled the fecal microbiota in matched HSPC and CRPC from 21 patients who received ADT at our urological center using 16S rRNA gene amplicon sequencing. Differences in microbiota were determined with α/β-diversity and LefSe analysis. Functional inference of microbiota was performed with PICRUSt. Results: The results showed that the gut microbial community in CRPC was significantly altered with increased abundance of several bacterial flora including genus Phascolarctobacterium and Ruminococcus. For functional analyses, bacterial gene pathways involved in terpenoids/polyketides metabolism and ether lipid metabolism were significantly activated in CRPC. Conclusions: Measurable differences in the gut microbiota were identified between HSPC and CRPC. Functional validations are further needed to ascertain the underlying mechanism of these differential microbiota in the process of CRPC, and their potential as new targets to enhance ADT responses.