Abstract P001: The gut microbiome-prostate tumor crosstalk is modulated by dietary polyunsaturated fatty acids
Notice bibliographique
Résumé
Abstract Introduction and Objective: Recently, gut microbiota emerged as an important factor for success of immunity-based cancer treatments. However, its steady-state interaction and contribution to developing tumors is largely unexplored in non-intestinal cancers. Our objective was to investigate the connection between prostate tumor and the gut microbiota independently of cancer therapies. Methods: Human fecal samples were obtained from men participating into a phase IIb double-blind randomized controlled trial testing 3g/day of monoglyceride-eicosapentaenoic acid (MAG-EPA) versus placebo for a 4-10 week period before their radical prostatectomy (NCT02333435). A second set of samples were from men taking the same intervention of MAG-EPA or placebo after a PSA increase following their radical prostatectomy (NCT03753334). Short chain fatty acids (SCFA) analysis of patient stool samples between baseline and surgery was performed by gas chromatography coupled with flame ionization detection. 16srRNA libraries were amplified by targeting a fragment of the V3-V4 hypervariable region of the bacterial 16S rRNA gene. High-throughput sequencing of the bar-coded amplicons was performed on a MiSeq apparatus and the bioinformatics analysis was conducted using Mothur pipeline. In addition to human fecal samples, fully immunocompetent C57BL/6 mice were injected subcutaneously with TRAMP-C2 or PTEN−/− or PTEN−/− RB1−/− mouse prostate cancer cells to measure changes in the gut microbiota during tumor growth. We also recapitulated the MAG-EPA intervention in our TRAMP-C2 mice model and fed by gavage four different fatty acids (omega-9 (high oleic sunflower oil), omega-6 (MAG-arachidonic acid) and two omega-3 (MAG-docosahexaenoic and MAG-EPA). Results: In human fecal samples from prostate cancer patients, we observed a reduced gut microbiota diversity correlating with tumor stage. We also found that tumor growth was sufficient to modulate the microbiota in three independent prostate cancer syngeneic mouse models. We showed that transplanted human gut flora was sufficient to modulate ectopic prostate tumor growth, supporting the causal impact of gut microbiota for prostate cancer. The analysis of SCFA in patient stool samples between baseline and surgery showed that MAG-EPA prebiotic intervention was associated with a decrease of fecal butyric acid levels in prostate cancer patients with downgrade at surgery. We finally investigated this gut-tumor connection using purified polyunsaturated fatty acids prebiotics in patients and mice. We observed a reduction in the levels of Ruminococcaceae following dietary omega-3 supplementation that correlated with prostate cancer downgrade in patients and reduced tumor growth in mice. Conclusion: Overall our findings suggest that diet-actionable components of the gut microbiome can regulate prostate cancer growth. Citation Format: Jalal Laaraj, Gabriel Lachance, Nikunj Gevariya, Thibaut Varin, Andrei Feldiorean, Fanny Gaignier, Isabelle Boudreau Julien, Hui Wen Xu, Tarek Hallal, Jean-François Pelletier, Sidki Bouslama, Nadia Boufaied, Nicolas Derome, Yves Fradet, Leigh Ellis, Ciriaco A. Piccirillo, Frédéric Raymond, David P. Labbé, Alain Bergeron, André Marette, Karine Robitaille, Vincent Fradet. The gut microbiome-prostate tumor crosstalk is modulated by dietary polyunsaturated fatty acids [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P001.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».