Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

L B Bindels, P Porporato, E M Dewulf, J Verrax, A M Neyrinck, J C Martin, K P Scott, P Buc Calderon, O Feron, G G Muccioli, P Sonveaux, P D Cani, N M Delzenne

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Abstract

background: Metabolites released by the gut microbiota may influence host metabolism and immunity. We have tested the hypothesis that inulin-type fructans (ITF), by promoting microbial production of short-chain fatty acids (SCFA), influence cancer cell proliferation outside the gut.
methods: Mice transplanted with Bcr-Abl-transfected BaF3 cells, received ITF in their drinking water. Gut microbiota was analysed by 16S rDNA polymerase chain reaction (PCR)–denaturing gradient gel electrophoresis (DGGE) and qPCR. Serum Short-chain fatty acids were quantified by UHPLC-MS. Cell proliferation was evaluated in vivo, by molecular biology and histology, and in vitro.
results: Inulin-type fructans treatment reduces hepatic BaF3 cell infiltration, lessens inflammation and increases portal propionate concentration. In vitro, propionate reduces BaF3 cell growth through a cAMP level-dependent pathway. Furthermore, the activation of free fatty acid receptor 2 (FFA2), a Gi/Gq-protein-coupled receptor also known as GPR43 and that binds propionate, lessens the proliferation of BaF3 and other human cancer cell lines.
conclusion: We show for the first time that the fermentation of nutrients such as ITF into propionate can counteract malignant cell proliferation in the liver tissue. Our results support the interest of FFA2 activation as a new strategy for cancer therapeutics. This study highlights the importance of research focusing on gut microbes–host interactions for managing systemic and severe diseases such as leukaemia.
Original languageEnglish
Pages (from-to)1337-1344
Number of pages8
JournalBritish Journal of Cancer
Volume107
Issue number8
Early online date13 Sep 2012
DOIs
Publication statusPublished - 9 Oct 2012

Fingerprint

Fructans
Inulin
Propionates
Cell Proliferation
Volatile Fatty Acids
Liver
Nonesterified Fatty Acids
Neoplasms
Gq-G11 GTP-Binding Protein alpha Subunits
Denaturing Gradient Gel Electrophoresis
Ribosomal DNA
Drinking Water
Fermentation
Molecular Biology
Hepatocytes
Immunity
Histology
Leukemia
Inflammation
Cell Line

Keywords

  • gut microbiota
  • propionate
  • cancer cells
  • FFA2/FFAR2/GPR43
  • inulin-type fructans

Cite this

Bindels, L. B., Porporato, P., Dewulf, E. M., Verrax, J., Neyrinck, A. M., Martin, J. C., ... Delzenne, N. M. (2012). Gut microbiota-derived propionate reduces cancer cell proliferation in the liver. British Journal of Cancer, 107(8), 1337-1344. https://doi.org/10.1038/bjc.2012.409

Gut microbiota-derived propionate reduces cancer cell proliferation in the liver. / Bindels, L B; Porporato, P; Dewulf, E M; Verrax, J; Neyrinck, A M; Martin, J C; Scott, K P; Buc Calderon, P; Feron, O; Muccioli, G G; Sonveaux, P; Cani, P D; Delzenne, N M.

In: British Journal of Cancer, Vol. 107, No. 8, 09.10.2012, p. 1337-1344.

Research output: Contribution to journalArticle

Bindels, LB, Porporato, P, Dewulf, EM, Verrax, J, Neyrinck, AM, Martin, JC, Scott, KP, Buc Calderon, P, Feron, O, Muccioli, GG, Sonveaux, P, Cani, PD & Delzenne, NM 2012, 'Gut microbiota-derived propionate reduces cancer cell proliferation in the liver', British Journal of Cancer, vol. 107, no. 8, pp. 1337-1344. https://doi.org/10.1038/bjc.2012.409
Bindels LB, Porporato P, Dewulf EM, Verrax J, Neyrinck AM, Martin JC et al. Gut microbiota-derived propionate reduces cancer cell proliferation in the liver. British Journal of Cancer. 2012 Oct 9;107(8):1337-1344. https://doi.org/10.1038/bjc.2012.409
Bindels, L B ; Porporato, P ; Dewulf, E M ; Verrax, J ; Neyrinck, A M ; Martin, J C ; Scott, K P ; Buc Calderon, P ; Feron, O ; Muccioli, G G ; Sonveaux, P ; Cani, P D ; Delzenne, N M. / Gut microbiota-derived propionate reduces cancer cell proliferation in the liver. In: British Journal of Cancer. 2012 ; Vol. 107, No. 8. pp. 1337-1344.
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AU - Scott, K P

AU - Buc Calderon, P

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N2 - background: Metabolites released by the gut microbiota may influence host metabolism and immunity. We have tested the hypothesis that inulin-type fructans (ITF), by promoting microbial production of short-chain fatty acids (SCFA), influence cancer cell proliferation outside the gut.methods: Mice transplanted with Bcr-Abl-transfected BaF3 cells, received ITF in their drinking water. Gut microbiota was analysed by 16S rDNA polymerase chain reaction (PCR)–denaturing gradient gel electrophoresis (DGGE) and qPCR. Serum Short-chain fatty acids were quantified by UHPLC-MS. Cell proliferation was evaluated in vivo, by molecular biology and histology, and in vitro.results: Inulin-type fructans treatment reduces hepatic BaF3 cell infiltration, lessens inflammation and increases portal propionate concentration. In vitro, propionate reduces BaF3 cell growth through a cAMP level-dependent pathway. Furthermore, the activation of free fatty acid receptor 2 (FFA2), a Gi/Gq-protein-coupled receptor also known as GPR43 and that binds propionate, lessens the proliferation of BaF3 and other human cancer cell lines.conclusion: We show for the first time that the fermentation of nutrients such as ITF into propionate can counteract malignant cell proliferation in the liver tissue. Our results support the interest of FFA2 activation as a new strategy for cancer therapeutics. This study highlights the importance of research focusing on gut microbes–host interactions for managing systemic and severe diseases such as leukaemia.

AB - background: Metabolites released by the gut microbiota may influence host metabolism and immunity. We have tested the hypothesis that inulin-type fructans (ITF), by promoting microbial production of short-chain fatty acids (SCFA), influence cancer cell proliferation outside the gut.methods: Mice transplanted with Bcr-Abl-transfected BaF3 cells, received ITF in their drinking water. Gut microbiota was analysed by 16S rDNA polymerase chain reaction (PCR)–denaturing gradient gel electrophoresis (DGGE) and qPCR. Serum Short-chain fatty acids were quantified by UHPLC-MS. Cell proliferation was evaluated in vivo, by molecular biology and histology, and in vitro.results: Inulin-type fructans treatment reduces hepatic BaF3 cell infiltration, lessens inflammation and increases portal propionate concentration. In vitro, propionate reduces BaF3 cell growth through a cAMP level-dependent pathway. Furthermore, the activation of free fatty acid receptor 2 (FFA2), a Gi/Gq-protein-coupled receptor also known as GPR43 and that binds propionate, lessens the proliferation of BaF3 and other human cancer cell lines.conclusion: We show for the first time that the fermentation of nutrients such as ITF into propionate can counteract malignant cell proliferation in the liver tissue. Our results support the interest of FFA2 activation as a new strategy for cancer therapeutics. This study highlights the importance of research focusing on gut microbes–host interactions for managing systemic and severe diseases such as leukaemia.

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