title: Non Digestible Oligosaccharides Modulate the Gut Microbiota to Control the Development of Leukemia and Associated Cachexia in Mice.
abstract: We tested the hypothesis that changing the gut microbiota using pectic oligosaccharides (POS) or inulin (INU) differently modulates the progression of leukemia and related metabolic disorders. Mice were transplanted with Bcr-Abl-transfected proB lymphocytes mimicking leukemia and received either POS or INU in their diet (5%) for 2 weeks. Combination of pyrosequencing, PCR-DGGE and qPCR analyses of the 16S rRNA gene revealed that POS decreased microbial diversity and richness of caecal microbiota whereas it increased Bifidobacterium spp., Roseburia spp. and Bacteroides spp. (affecting specifically B. dorei) to a higher extent than INU. INU supplementation increased the portal SCFA propionate and butyrate, and decreased cancer cell invasion in the liver. POS treatment did not affect hepatic cancer cell invasion, but was more efficient than INU to decrease the metabolic alterations. Indeed, POS better than INU delayed anorexia linked to cancer progression. In addition, POS treatment increased acetate in the caecal content, changed the fatty acid profile inside adipose tissue and counteracted the induction of markers controlling β-oxidation, thereby hampering fat mass loss. Non digestible carbohydrates with prebiotic properties may constitute a new nutritional strategy to modulate gut microbiota with positive consequences on cancer progression and associated cachexia.
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Laure B
authors.initials: LB
authors.lastname: Bindels
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Audrey M
authors.initials: AM
authors.lastname: Neyrinck
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Nuria
authors.initials: N
authors.lastname: Salazar
authors.affiliation: Fundamental and Applied Research for Animal and Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Sart Tilman, Liège, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Taminiau
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Céline
authors.initials: C
authors.lastname: Druart
authors.affiliation: Bioanalysis and Pharmacology of Bioactive Lipids lab, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Giulio G
authors.initials: GG
authors.lastname: Muccioli
authors.affiliation: Department of Chemistry and Bio-industry, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: François
authors.affiliation: Department of Chemistry and Bio-industry, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Blecker
authors.affiliation: Department of Chemistry and Bio-industry, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium.
authors.forename: Aurore
authors.initials: A
authors.lastname: Richel
authors.affiliation: Fundamental and Applied Research for Animal and Health (FARAH), Faculty of Veterinary Medicine, University of Liège, Sart Tilman, Liège, Belgium.
authors.forename: Georges
authors.initials: G
authors.lastname: Daube
authors.affiliation: Laboratory of Food and Environmental Microbiology, Earth and Life Institute, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Mahillon
authors.affiliation: Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias, (IPLA-CSIC), Villaviciosa, Asturias, Spain.
authors.forename: Clara G
authors.initials: CG
authors.lastname: de los Reyes-Gavilán
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium; Walloon Excellence in Life sciences and BIOtechnology (WELBIO), Louvain Drug Research Institute, UCL, B-1200 Brussels, Belgium.
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.affiliation: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Delzenne
mesh_terms: D000085:Acetates / Q000378:metabolism; D000818:Animals; D001439:Bacteroides / Q000187:drug effects; D001644:Bifidobacterium / Q000187:drug effects; D002100:Cachexia / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D002432:Cecum / Q000187:drug effects / Q000382:microbiology*; D002478:Cells, Cultured; D019587:Dietary Supplements; D018450:Disease Progression; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000235:genetics; D007444:Inulin / Q000008:administration & dosage; D007938:Leukemia / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D064307:Microbiota / Q000187:drug effects*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009844:Oligosaccharides / Q000008:administration & dosage*; D012336:RNA, Ribosomal, 16S / Q000235:genetics
chemical_list: D000085:Acetates; D009844:Oligosaccharides; D012336:RNA, Ribosomal, 16S; D007444:Inulin