title: Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemic mice with cachexia.
abstract: Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and 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: Department of Food and Nutritional Sciences, University of Reading, Reading, UK.
authors.forename: Sandrine P
authors.initials: SP
authors.lastname: Claus
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, Reading, UK.
authors.forename: Caroline I
authors.initials: CI
authors.lastname: Le Roy
authors.affiliation: Lactic Acid Bacteria and Mucosal Immunity, Centre for Infection and Immunity of Lille, INSERM U1019-CNRS UMR 8204, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Grangette
authors.affiliation: Lactic Acid Bacteria and Mucosal Immunity, Centre for Infection and Immunity of Lille, INSERM U1019-CNRS UMR 8204, Institut Pasteur de Lille, Université Lille Nord de France, Lille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Pot
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Inés
authors.initials: I
authors.lastname: Martinez
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.|Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jens
authors.initials: J
authors.lastname: Walter
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, 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: D000208:Acute Disease; D000818:Animals; D041963:Bacteroidetes / Q000187:drug effects / Q000254:growth & development; D002100:Cachexia / Q000382:microbiology* / Q000628:therapy; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000382:microbiology* / Q000628:therapy; D004195:Disease Models, Animal; D004755:Enterobacteriaceae / Q000187:drug effects / Q000254:growth & development; D005260:Female; D005630:Fructans / Q000008:administration & dosage; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000502:physiology*; D006706:Homeostasis; D007249:Inflammation; D007422:Intestines / Q000382:microbiology; D007444:Inulin / Q000008:administration & dosage; D007778:Lactobacillus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D007938:Leukemia / Q000382:microbiology* / Q000628:therapy; D055432:Metabolomics; D051379:Mice; D008807:Mice, Inbred BALB C; D058616:Synbiotics / Q000008:administration & dosage*
chemical_list: D005630:Fructans; D007444:Inulin