title: Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model.
abstract: The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl), characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis) in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L) in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay). These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle.
authors: Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.
authors: Laure B
authors: LB
authors: Bindels
authors: Raphaël
authors: R
authors: Beck
authors: Olivier
authors: O
authors: Schakman
authors: Jennifer C
authors: JC
authors: Martin
authors: Fabienne
authors: F
authors: De Backer
authors: Florence M
authors: FM
authors: Sohet
authors: Evelyne M
authors: EM
authors: Dewulf
authors: Barbara D
authors: BD
authors: Pachikian
authors: Audrey M
authors: AM
authors: Neyrinck
authors: Jean-Paul
authors: JP
authors: Thissen
authors: Julien
authors: J
authors: Verrax
authors: Pedro Buc
authors: PB
authors: Calderon
authors: Bruno
authors: B
authors: Pot
authors: Corinne
authors: C
authors: Grangette
authors: Patrice D
authors: PD
authors: Cani
authors: Karen P
authors: KP
authors: Scott
authors: Nathalie M
authors: NM
authors: Delzenne
mesh_terms: D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D041981:Gastrointestinal Tract / Q000382:microbiology; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism*; D007778:Lactobacillus / Q000502:physiology*; D007942:Leukemia, Experimental / Q000150:complications* / Q000235:genetics / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D054892:Metagenome; D051379:Mice; D008807:Mice, Inbred BALB C; D009133:Muscular Atrophy / Q000209:etiology / Q000517:prevention & control*; D054448:Precursor Cells, B-Lymphoid / Q000637:transplantation; D013160:Splenic Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; D016044:Fusion Proteins, bcr-abl