TY - JOUR T1 - The Quorum Sensing Peptide EntF* Promotes Colorectal Cancer Metastasis in Mice: A New Factor in the Microbiome-Host Interaction JF - bioRxiv DO - 10.1101/2020.09.17.301044 SP - 2020.09.17.301044 AU - Nathan Debunne AU - Evelien Wynendaele AU - Yorick Janssens AU - Anton De Spiegeleer AU - Frederick Verbeke AU - Liesa Tack AU - Sophie Van Welden AU - Evy Goossens AU - Daniel Knappe AU - Ralf Hoffmann AU - Christophe Van De Wiele AU - Debby Laukens AU - Peter Van Eenoo AU - Filip Van Immerseel AU - Olivier De Wever AU - Bart De Spiegeleer Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/09/18/2020.09.17.301044.abstract N2 - Background Colorectal cancer, one of the most common malignancies worldwide, is associated with a high mortality rate, mainly caused by metastasis. Comparative metagenome-wide analyses between healthy individuals and cancer patients suggest a role for the human intestinal microbiota. Nevertheless, which microbial molecules are involved in this communication is largely unknown, with current studies mainly focusing on short chain fatty acids and amino acid metabolites as potential mediators. However, quorum sensing peptides are not yet considered in this microbiome-host interaction: their in vivo presence nor any in vivo host-effect have been reported.Results For the first time, we showed that a quorum sensing peptide metabolite, EntF* produced by intestinal microbiota (E. faecium), is present in the blood circulation of mice. Moreover, it significantly promotes colorectal cancer metastasis in vivo, with metastatic lesions found in both liver and lung tissues, using an orthotopic mice model evaluating bioluminescence as well as macroscopic and microscopic presence of metastatic tumour nodules. In vitro tests on E-cadherin expression levels thereby indicated that the first, second, sixth and tenth amino acid of EntF* were critical for the epithelial-mesenchymal transition (EMT) effect, responsible for tumour metastasis.Conclusion This paper adds a new group of molecules, the quorum sensing peptides, as an additional causative factor explaining the microbiome-host interaction. The presence of a selected quorum sensing peptide (metabolite) in the mouse was proven for the first time and its in vivo effect on colorectal metastasis was demonstrated. We anticipate our in vivo results to be a starting point for broader microbiome-health investigations, not only limited to colorectal cancer metastasis, but also for developing novel bio-therapeutics in other disease areas, giving due attention to the QSP produced by the microbiome.Competing Interest StatementThe authors have declared no competing interest. ER -