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1. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis.

Author

Pernigoni N, Zagato E, Calcinotto A, Troiani M, Mestre RP, Calì B, Attanasio G, Troisi J, Minini M, Mosole S, Revandkar A, Pasquini E, Elia AR, Bossi D, Rinaldi A, Rescigno P, Flohr P, Hunt J, Neeb A, Buroni L, Guo C, Welti J, Ferrari M, Grioni M, Gauthier J, Gharaibeh RZ, Palmisano A, Lucchini GM, D'Antonio E, Merler S, Bolis M, Grassi F, Esposito A, Bellone M, Briganti A, Rescigno M, Theurillat JP, Jobin C, Gillessen S, de Bono J, and Alimonti A

Subjects
Aged, Aged, 80 and over, Androgen Antagonists therapeutic use, Animals, Anti-Bacterial Agents pharmacology, Bacteria drug effects, Bacteria genetics, Cell Line, Tumor, Fecal Microbiota Transplantation, Gastrointestinal Microbiome drug effects, Gastrointestinal Microbiome genetics, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Middle Aged, Neoplasms, Experimental, Prevotella metabolism, Prostatic Neoplasms, Castration-Resistant drug therapy, Symbiosis, Xenograft Model Antitumor Assays, Androgens biosynthesis, Bacteria metabolism, Gastrointestinal Microbiome physiology, Host Microbial Interactions, Prostatic Neoplasms, Castration-Resistant metabolism, Prostatic Neoplasms, Castration-Resistant microbiology
Abstract

The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of castration resistance in mice. Specifically, the intestinal microbial community in mice and patients with CRPC was enriched for species capable of converting androgen precursors into active androgens. Ablation of the gut microbiota by antibiotic therapy delayed the emergence of castration resistance even in immunodeficient mice. Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. In contrast, tumor growth was controlled by FMT from hormone-sensitive prostate cancer patients and Prevotella stercorea administration. These results reveal that the commensal gut microbiota contributes to endocrine resistance in CRPC by providing an alternative source of androgens.

Published
2021
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2. Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis

Author

Angela Rita Elia, Penny Flohr, Martina Troiani, Silke Gillessen, Matteo Grioni, Maria Rescigno, Alberto Briganti, Daniela Bossi, Simone Mosole, Lorenzo Buroni, Christina Guo, Christian Jobin, Anna Palmisano, Eugenia D’Antonio, Mirko Minini, Antonio Esposito, Antje Neeb, Emiliano Pasquini, Pasquale Rescigno, Jonathan Welti, Bianca Calì, Gladys Martinetti Lucchini, Jacopo Troisi, Nicolò Pernigoni, Andrea Alimonti, Giuseppe Attanasio, Sara Merler, Andrea Rinaldi, Josee Gauthier, Jean-Philippe Theurillat, Ajinkya Revandkar, Raad Z. Gharaibeh, Johann S. de Bono, Matteo Ferrari, Elena Zagato, Ricardo Pereira Mestre, Marco Bolis, Joanne Hunt, Fabio Grassi, Matteo Bellone, Arianna Calcinotto, Pernigoni, N., Zagato, E., Calcinotto, A., Troiani, M., Mestre, R. P., Cali, B., Attanasio, G., Troisi, J., Minini, M., Mosole, S., Revandkar, A., Pasquini, E., Elia, A. R., Bossi, D., Rinaldi, A., Rescigno, P., Flohr, P., Hunt, J., Neeb, A., Buroni, L., Guo, C., Welti, J., Ferrari, M., Grioni, M., Gauthier, J., Gharaibeh, R. Z., Palmisano, A., Lucchini, G. M., D'Antonio, E., Merler, S., Bolis, M., Grassi, F., Esposito, A., Bellone, M., Briganti, A., Rescigno, M., Theurillat, J. -P., Jobin, C., Gillessen, S., de Bono, J., and Alimonti, A.

Subjects
Aged, Aged, 80 and over, Androgen Antagonists, Androgens, Animals, Anti-Bacterial Agents, Bacteria, Cell Line, Tumor, Fecal Microbiota Transplantation, Gastrointestinal Microbiome, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, SCID, Middle Aged, Neoplasms, Experimental, Prevotella, Prostatic Neoplasms, Castration-Resistant, Symbiosis, Xenograft Model Antitumor Assays, Host Microbial Interactions, Microbial metabolism, Gut flora, Castration-Resistant, SCID, Inbred C57BL, urologic and male genital diseases, Cell Line, Microbiology, Experimental, Prostate cancer, Neoplasms, 80 and over, medicine, Tumor, Multidisciplinary, biology, Host (biology), Prostatic Neoplasms, biology.organism_classification, medicine.disease, Commensalism, Inbred NOD
Abstract

The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of castration resistance in mice. Specifically, the intestinal microbial community in mice and patients with CRPC was enriched for species capable of converting androgen precursors into active androgens. Ablation of the gut microbiota by antibiotic therapy delayed the emergence of castration resistance even in immunodeficient mice. Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. In contrast, tumor growth was controlled by FMT from hormone-sensitive prostate cancer patients and Prevotella stercorea administration. These results reveal that the commensal gut microbiota contributes to endocrine resistance in CRPC by providing an alternative source of androgens.

Published
2021

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