[HTML][HTML] Gut microbiota-derived propionate reduces cancer cell proliferation in the liver
LB Bindels, P Porporato, EM Dewulf, J Verrax… - British journal of …, 2012 - nature.com
British journal of cancer, 2012•nature.com
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 …
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 …
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.
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