The gut microbial metabolite formate exacerbates colorectal cancer progression

Ternes, Dominik; Tsenkova, Mina; Pozdeev, Vitaly; Meyers, Marianne; Koncina, Eric; Atatri, Sura; Schmitz, Martine; Karta, Jessica; Schmoetten, Maryse; Heinken, Almut; Rodriguez, Fabien; Delbrouck, Catherine; Gaigneaux, Anthoula; Ginolhac, Aurélien; Dan Nguyen, Tam Thuy; Grandmougin, Lea; Frachet-Bour, Audrey; Martin-Gallausiaux, Camille; Pires Pacheco, Maria Irene; Neuberger-Castillo, Lorie; Miranda, Paulo; Zuegel, Nikolaus; Ferrand, Jean-Yves; Gantenbein, Manon; Sauter, Thomas; Slade, Daniel Joseph; Thiele, Ines; Meiser, Johannes; Haan, Serge; Wilmes, Paul; Letellier, Elisabeth

doi:10.1038/s42255-022-00558-0

Reference : The gut microbial metabolite formate exacerbates colorectal cancer progression


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	Focus Areas :	Systems Biomedicine
	To cite this reference:	http://hdl.handle.net/10993/51992

Title :	The gut microbial metabolite formate exacerbates colorectal cancer progression
Language :	English
Author, co-author :	Ternes, Dominik [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Tsenkova, Mina [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Pozdeev, Vitaly [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Meyers, Marianne [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Koncina, Eric [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Atatri, Sura [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Schmitz, Martine [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Karta, Jessica [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Schmoetten, Maryse [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Heinken, Almut [School of Medicine, National University of Ireland, Galway, Ireland. > > > ; Ryan Institute, National University of Galway, Galway, Ireland.]
	Rodriguez, Fabien [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Delbrouck, Catherine [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Gaigneaux, Anthoula [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Ginolhac, Aurélien [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Dan Nguyen, Tam Thuy [Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.]
	Grandmougin, Lea [Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.]
	Frachet-Bour, Audrey [Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.]
	Martin-Gallausiaux, Camille [Systems Ecology Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg]
	Pires Pacheco, Maria Irene [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Neuberger-Castillo, Lorie [Integrated BioBank of Luxembourg, Dudelange, Luxembourg]
	Miranda, Paulo [National Center of Pathology, Laboratoire National de Santé, Dudelange, Luxembourg]
	Zuegel, Nikolaus [Department of Surgery, Centre Hospitalier Emile Mayrisch, Esch-sur-Alzette, Luxembourg]
	Ferrand, Jean-Yves [Clinical and Epidemiological Investigation Center, Department of Population Health, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Gantenbein, Manon [Clinical and Epidemiological Investigation Center, Department of Population Health, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Sauter, Thomas [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Slade, Daniel Joseph [Department of Biochemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA]
	Thiele, Ines [School of Medicine, National University of Ireland, Galway, Ireland > > > ; Ryan Institute, National University of Galway, Galway, Ireland.]
	Meiser, Johannes [Cancer Metabolism Group, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg]
	Haan, Serge [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
	Wilmes, Paul [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Systems Ecology >]
	Letellier, Elisabeth [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) >]
Publication date :	4-Apr-2022
Journal title :	Nature Metabolism
Publisher :	Springer Nature
Peer reviewed :	Yes (verified by ORBi^lu)
Audience :	International
e-ISSN :	2522-5812
City :	Berlin
Country :	Germany
Keywords :	[en] Gut microbiome ; Colorectal cancer ; Formate
Abstract :	[en] The gut microbiome is a key player in the immunomodulatory and protumorigenic microenvironment during colorectal cancer (CRC), as different gut-derived bacteria can induce tumour growth. However, the crosstalk between the gut microbiome and the host in relation to tumour cell metabolism remains largely unexplored. Here we show that formate, a metabolite produced by the CRC-associated bacterium Fusobacterium nucleatum, promotes CRC development. We describe molecular signatures linking CRC phenotypes with Fusobacterium abundance. Cocultures of F. nucleatum with patient-derived CRC cells display protumorigenic effects, along with a metabolic shift towards increased formate secretion and cancer glutamine metabolism. We further show that microbiome-derived formate drives CRC tumour invasion by triggering AhR signalling, while increasing cancer stemness. Finally, F. nucleatum or formate treatment in mice leads to increased tumour incidence or size, and Th17 cell expansion, which can favour proinflammatory profiles. Moving beyond observational studies, we identify formate as a gut-derived oncometabolite that is relevant for CRC progression.
Funders :	Fonds National de la Recherche - FnR, Fondation Cancer, Fondation du Pélican de Mie and Pierre Hippert-Faber
Target :	Researchers
Permalink :	http://hdl.handle.net/10993/51992
DOI :	10.1038/s42255-022-00558-0
FnR project :	FnR ; FNR11282028 > Elisabeth Letellier > miRMet > Role Of Mir-371-373 Cluster In Tumor Initiation And Metastatic Colonization > 15/03/2017 > 14/07/2020 > 2016

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