The gut microbiota modulates response to hormonal treatments in prostate cancer (PCa) patients, but whether it influences PCa progression remains unknown. Here, we show a reduction in fecal microbiota alpha-diversity correlating with increase tumour burden in two distinct groups of hormonotherapy naïve PCa patients and three murine PCa models. Fecal microbiota transplantation (FMT) from patients with high PCa volume is sufficient to stimulate the growth of mouse PCa revealing the existence of a gut microbiome-cancer crosstalk. Analysis of gut microbial-related pathways in mice with aggressive PCa identifies three enzymes responsible for the metabolism of long-chain fatty acids (LCFA). Supplementation with LCFA omega-3 MAG-EPA is sufficient to reduce PCa growth in mice and cancer up-grading in pre-prostatectomy PCa patients correlating with a reduction of gut Ruminococcaceae in both and fecal butyrate levels in PCa patients. This suggests that the beneficial effect of omega-3 rich diet is mediated in part by modulating the crosstalk between gut microbes and their metabolites in men with PCa.
Nature communications. 2024 Apr 23*** epublish ***
Gabriel Lachance, Karine Robitaille, Jalal Laaraj, Nikunj Gevariya, Thibault V Varin, Andrei Feldiorean, Fanny Gaignier, Isabelle Bourdeau Julien, Hui Wen Xu, Tarek Hallal, Jean-François Pelletier, Sidki Bouslama, Nadia Boufaied, Nicolas Derome, Alain Bergeron, Leigh Ellis, Ciriaco A Piccirillo, Frédéric Raymond, Yves Fradet, David P Labbé, André Marette, Vincent Fradet
Laboratoire d'Uro-Oncologie Expérimentale, Oncology Axis, Centre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada., Centre de recherche de l'IUCPQ, Québec, QC, Canada., Cancer Research Program, Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Institute of nutrition and functional foods (INAF) and NUTRISS Center - Nutrition, health and society of Université Laval, Québec, QC, Canada., Department of Mathematics and Statistics, Université Laval, Québec, QC, Canada., Institut de Biologie Intégrative et des Systèmes (IBIS), Université Laval, Québec, QC, Canada., Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA., Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montréal, QC, Canada., Laboratoire d'Uro-Oncologie Expérimentale, Oncology Axis, Centre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada. .