title: Gut microbiota-derived propionate reduces cancer cell proliferation in the liver.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: L B
authors.initials: LB
authors.lastname: Bindels
authors.forename: P
authors.initials: P
authors.lastname: Porporato
authors.forename: E M
authors.initials: EM
authors.lastname: Dewulf
authors.forename: J
authors.initials: J
authors.lastname: Verrax
authors.forename: A M
authors.initials: AM
authors.lastname: Neyrinck
authors.forename: J C
authors.initials: JC
authors.lastname: Martin
authors.forename: K P
authors.initials: KP
authors.lastname: Scott
authors.forename: P
authors.initials: P
authors.lastname: Buc Calderon
authors.forename: O
authors.initials: O
authors.lastname: Feron
authors.forename: G G
authors.initials: GG
authors.lastname: Muccioli
authors.forename: P
authors.initials: P
authors.lastname: Sonveaux
authors.forename: P D
authors.initials: PD
authors.lastname: Cani
authors.forename: N M
authors.initials: NM
authors.lastname: Delzenne
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004032:Diet; D004195:Disease Models, Animal; D005232:Fatty Acids, Volatile / Q000378:metabolism; D005260:Female; D005630:Fructans / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D007422:Intestines / Q000382:microbiology*; D007938:Leukemia / Q000378:metabolism*; D008099:Liver / Q000473:pathology*; D054892:Metagenome / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D056692:Prebiotics; D011422:Propionates / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*
chemical_list: D005232:Fatty Acids, Volatile; C506481:Ffar2 protein, mouse; D005630:Fructans; D056692:Prebiotics; D011422:Propionates; D043562:Receptors, G-Protein-Coupled; C029658:propionic acid