The gut microbial metabolite formate exacerbates colorectal cancer progression

[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.

Research center :

ULHPC - University of Luxembourg: High Performance Computing

Disciplines :

Biochemistry, biophysics & molecular biology

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.

More authors (21 more)

External co-authors :

yes

Language :

English

Title :

The gut microbial metabolite formate exacerbates colorectal cancer progression

Publication date :

04 April 2022

Journal title :

Nature Metabolism

eISSN :

2522-5812

Publisher :

Springer Nature, Berlin, Germany

Peer reviewed :

Peer Reviewed verified by ORBi

Focus Area :

Systems Biomedicine

FnR Project :

FNR11282028 - Role Of Mir-371-373 Cluster In Tumor Initiation And Metastatic Colonization, 2016 (15/03/2017-14/07/2020) - Elisabeth Letellier

Funders :

Fonds National de la Recherche - FnR, Fondation Cancer, Fondation du Pélican de Mie and Pierre Hippert-Faber

Available on ORBilu :

since 01 September 2022

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