{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:07:31Z","timestamp":1792789651924,"version":"4.5.0"},"reference-count":55,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation of Urological Research","award":["Leonardo de la Pe\u00f1a 2022 Grant"],"award-info":[{"award-number":["Leonardo de la Pe\u00f1a 2022 Grant"]}]},{"name":"Galician Urology Society"},{"name":"Axencia Galega de Innovaci\u00f3n","award":["GAIN IN607B-2022-19"],"award-info":[{"award-number":["GAIN IN607B-2022-19"]}],"id":[{"id":"https:\/\/ror.org\/02vcxyt85","id-type":"ROR","asserted-by":"crossref"}]},{"award":["GAIN IN607B-2022-19"],"award-info":[{"award-number":["GAIN IN607B-2022-19"]}],"id":[{"id":"https:\/\/ror.org\/02vcxyt85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Metastatic prostate cancer (MPCa) remains an aggressive disease despite the introduction of androgen receptor pathway inhibitors (ARPIs), and biomarkers predicting progression are still lacking. The aim of this study was to investigate gut microbiota (GM) composition and functional potential associated with advanced disease and progression under ARPI therapy. The GM of 15 patients with metastatic PCa receiving ARPIs, including 5 patients with disease progression, was compared with that of 39 patients with untreated (UT) PCa using shallow shotgun metagenomic sequencing. The metastatic PCa cohort receiving ADT plus ARPI therapy showed reduced microbial alpha diversity and significant taxonomic and functional differences compared with the untreated, clinically localized PCa reference cohort. In patients with advanced disease, microbial functions related to dietary carbohydrate utilization, fermentation, epithelial interaction, and microbial structural maintenance were predominantly underrepresented, whereas stress-responsive and redox-associated functions were overrepresented. These alterations may reflect reduced metabolic and ecological versatility alongside increased adaptation to host-associated stress conditions. Compared with the UT group, in patients with progression we found that Bifidobacterium longum, Anaerobutyricum hallii, Ruminococcus sp., and Blautia obeum (LinDA coefficients 5.7, 2.6, 2.6 and 2.4, respectively) were enriched, whereas Sutterella wadsworthensis, Butyricimonas, Bilophila wadsworthia, Alistipes indistinctus, and Intestinimonas were depleted (LinDA coefficients \u22128.4, \u22125.9, \u22125, \u22125 and \u22123, respectively). Together, these findings identify distinct taxonomic and functional features associated with metastatic PCa under systemic therapy and microbial features observed in patients experiencing progression during ARPI treatment, providing potential candidates for biomarker development and generating testable hypotheses regarding microbiome\u2013host metabolic interactions in treatment resistance. The GM may therefore represent a potential source of biomarkers for advanced PCa and progression under ARPI therapy, although longitudinal and multi-omics studies are required to determine their predictive value and functional relevance.<\/jats:p>","DOI":"10.3390\/ijms27198454","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiota Signatures Associated with Metastatic Prostatic Cancer Treated with Androgen Receptor Pathway Inhibitor (ARPI) Therapy"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1734-1904","authenticated-orcid":false,"given":"Sonia","family":"P\u00e9rez-Castro","sequence":"first","affiliation":[{"name":"Microbiology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"},{"name":"Microbiology and Infectology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6810-3722","authenticated-orcid":false,"given":"Manuel","family":"Carballo-Quinta","sequence":"additional","affiliation":[{"name":"Urology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"},{"name":"Uropathology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5670-1898","authenticated-orcid":false,"given":"Nahir","family":"Rodr\u00edguez-Costas","sequence":"additional","affiliation":[{"name":"Microbiology and Infectology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain"},{"name":"Functional Biology and Health Sciences Department, Universidade de Vigo, 36310 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0479-8497","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Freire-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Urology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6952-2219","authenticated-orcid":false,"given":"Carlos","family":"Davina-Nunez","sequence":"additional","affiliation":[{"name":"Microbiology and Infectology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain"},{"name":"Functional Biology and Health Sciences Department, Universidade de Vigo, 36310 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Bellas-Pereira","sequence":"additional","affiliation":[{"name":"Urology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0139-9951","authenticated-orcid":false,"given":"Pablo","family":"Taboada-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Escuela T\u00e9cnica Superior de Ingenier\u00eda (ETSE), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"P\u00e9rez-Schoch","sequence":"additional","affiliation":[{"name":"Urology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0397-0868","authenticated-orcid":false,"given":"Jorge J.","family":"Cabrera-Alvargonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Microbiology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"},{"name":"Microbiology and Infectology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8423-5717","authenticated-orcid":false,"given":"Carlos A.","family":"Muller-Arteaga","sequence":"additional","affiliation":[{"name":"Urology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"},{"name":"Uropathology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1080-3599","authenticated-orcid":false,"given":"Juan F.","family":"S\u00e1nchez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Urology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Cesp\u00f3n-Outeda","sequence":"additional","affiliation":[{"name":"Urology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-6945","authenticated-orcid":false,"given":"M. Elena","family":"L\u00f3pez-D\u00edez","sequence":"additional","affiliation":[{"name":"Urology Department, Complexo Hospitalario Universitario de Vigo (CHUVI), 36312 Vigo, Spain"},{"name":"Uropathology Research Group, Galicia Sur Health Research Institute (IIS Galicia Sur), 36312 Vigo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","unstructured":"International Agency for Research on Cancer (IARC) (2024, December 07). Cancer Tomorrow. Available online: https:\/\/gco.iarc.who.int\/tomorrow."},{"key":"ref_2","unstructured":"International Agency for Research on Cancer (IARC) (2024, November 02). Global Cancer Observatory. Available online: https:\/\/gco.iarc.who.int\/."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Posdzich, P., Darr, C., Hilser, T., Wahl, M., Herrmann, K., Hadaschik, B., and Gr\u00fcnwald, V. (2023). 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