Gut microbiota signatures associated with advanced metastatic prostatic cancer treated with androgen receptor pathway inhibitor therapy

Metastatic prostate cancer (MPCa) is considered an aggressive condition. The objective was to elucidate the link between gut microbiota (GM) derived metabolites and disease progression in MPCa. Fecal microbiome shallow shotgun metagenomics of 15 patients with MPCa receiving ARPIs therapy were studied. A control group of 39 patients with non-advanced PCa was included. ARPIs-driven changes in the GM leading to functional redundancy in testosterone synthesis were observed. The GM could be contributing to epithelial–mesenchymal transition and MPCa progression by the increased synthesis of microbial-derived acetate. The feature-level analysis revealed that Bifidobacterium longum was enriched in the patients in a progression stage (LinDA coefficient 5.7) whereas Sutterella wadsworthensis, Butyricimonas, Bilophila wadsworthia, Alistipes indistinctus, Bacteroides thetaiotaomicron and Intestinimonas were depleted (LinDA coefficient -7.2, -5.1, -4.4, -3.9, -3.9 and -2.9, respectively). Bifidobacterium longum, Butyricimonas, Butyricimonas faecihominis, Bilophila sp. and Bacteroides thetaiotaomicron abundances were predictive of progression (AUC 0.88, 0.92, 0.88, 0.93 and 0.86, respectively, DESeq2; p < 0.00001). A deeper understanding of the multifaceted roles of intestinal microorganisms at various stages of the disease would be of crucial importance to achieve an overall perspective of the individual prognosis of MPCa.