A Everard

A M Neyrinck

AJ Brown

AS Neish

BF Hinnebusch

BL Pool-Zobel

C Cherbut

C Daubioul

C Sundstrom

E Le Poul

E M Dewulf

F Guarner

G G Muccioli

G Tolhurst

HS Taper

J Bray

J Busserolles

J C Martin

J Verrax

K P Scott

KM Maslowski

L B Bindels

LB Bindels

M Aoyama

M Montillo

MA Cox

MA Vinolo

N M Delzenne

NG Kondegowda

O Feron

P Buc Calderon

P D Cani

P Louis

P Porporato

P Sonveaux

PD Cani

R Alric

R Ren

S Siavoshian

T Lee

W Fiskus

Y Tang

Y Wang

YH Hong

British Journal of Cancer

English

PubMed

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

Bindels, Laure B.

Porporato, Paolo

Dewulf, Evelyne

Verrax, Julien

Neyrinck, Audrey M.

Martin, J C

Scott, K P

Buc Calderon, Pedro

Feron, Olivier

Muccioli, Giulio

Sonveaux, Pierre

Cani, Patrice D.

Delzenne, Nathalie M.

DIAL UCLouvain

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

Bindels, L B

Porporato, P

Dewulf, E M

Verrax, J

Neyrinck, A M

Buc Calderon, P

Feron, O

Muccioli, G G

Sonveaux, P

Cani, P D

Delzenne, N M

The Open University

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

Abstract

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DIAL UCLouvain

The Open University

Crossref