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The gut microbial metabolite formate exacerbates colorectal cancer progression

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 larg...

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Autores principales: Ternes, Dominik, Tsenkova, Mina, Pozdeev, Vitaly Igorevich, Meyers, Marianne, Koncina, Eric, Atatri, Sura, Schmitz, Martine, Karta, Jessica, Schmoetten, Maryse, Heinken, Almut, Rodriguez, Fabien, Delbrouck, Catherine, Gaigneaux, Anthoula, Ginolhac, Aurelien, Nguyen, Tam Thuy Dan, Grandmougin, Lea, Frachet-Bour, Audrey, Martin-Gallausiaux, Camille, Pacheco, Maria, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046088/
https://www.ncbi.nlm.nih.gov/pubmed/35437333
http://dx.doi.org/10.1038/s42255-022-00558-0
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author Ternes, Dominik
Tsenkova, Mina
Pozdeev, Vitaly Igorevich
Meyers, Marianne
Koncina, Eric
Atatri, Sura
Schmitz, Martine
Karta, Jessica
Schmoetten, Maryse
Heinken, Almut
Rodriguez, Fabien
Delbrouck, Catherine
Gaigneaux, Anthoula
Ginolhac, Aurelien
Nguyen, Tam Thuy Dan
Grandmougin, Lea
Frachet-Bour, Audrey
Martin-Gallausiaux, Camille
Pacheco, Maria
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
author_facet Ternes, Dominik
Tsenkova, Mina
Pozdeev, Vitaly Igorevich
Meyers, Marianne
Koncina, Eric
Atatri, Sura
Schmitz, Martine
Karta, Jessica
Schmoetten, Maryse
Heinken, Almut
Rodriguez, Fabien
Delbrouck, Catherine
Gaigneaux, Anthoula
Ginolhac, Aurelien
Nguyen, Tam Thuy Dan
Grandmougin, Lea
Frachet-Bour, Audrey
Martin-Gallausiaux, Camille
Pacheco, Maria
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
author_sort Ternes, Dominik
collection PubMed
description 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.
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spelling pubmed-90460882022-04-29 The gut microbial metabolite formate exacerbates colorectal cancer progression Ternes, Dominik Tsenkova, Mina Pozdeev, Vitaly Igorevich Meyers, Marianne Koncina, Eric Atatri, Sura Schmitz, Martine Karta, Jessica Schmoetten, Maryse Heinken, Almut Rodriguez, Fabien Delbrouck, Catherine Gaigneaux, Anthoula Ginolhac, Aurelien Nguyen, Tam Thuy Dan Grandmougin, Lea Frachet-Bour, Audrey Martin-Gallausiaux, Camille Pacheco, Maria 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 Nat Metab Article 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. Nature Publishing Group UK 2022-04-18 2022 /pmc/articles/PMC9046088/ /pubmed/35437333 http://dx.doi.org/10.1038/s42255-022-00558-0 Text en © The Author(s) 2022, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ternes, Dominik
Tsenkova, Mina
Pozdeev, Vitaly Igorevich
Meyers, Marianne
Koncina, Eric
Atatri, Sura
Schmitz, Martine
Karta, Jessica
Schmoetten, Maryse
Heinken, Almut
Rodriguez, Fabien
Delbrouck, Catherine
Gaigneaux, Anthoula
Ginolhac, Aurelien
Nguyen, Tam Thuy Dan
Grandmougin, Lea
Frachet-Bour, Audrey
Martin-Gallausiaux, Camille
Pacheco, Maria
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
The gut microbial metabolite formate exacerbates colorectal cancer progression
title The gut microbial metabolite formate exacerbates colorectal cancer progression
title_full The gut microbial metabolite formate exacerbates colorectal cancer progression
title_fullStr The gut microbial metabolite formate exacerbates colorectal cancer progression
title_full_unstemmed The gut microbial metabolite formate exacerbates colorectal cancer progression
title_short The gut microbial metabolite formate exacerbates colorectal cancer progression
title_sort gut microbial metabolite formate exacerbates colorectal cancer progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046088/
https://www.ncbi.nlm.nih.gov/pubmed/35437333
http://dx.doi.org/10.1038/s42255-022-00558-0
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