Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model

• Published in: PloS one Vol. 7; no. 6; p. e37971
• Main Authors: Bindels, Laure B, Beck, Raphaël, Schakman, Olivier, Martin, Jennifer C, De Backer, Fabienne, Sohet, Florence M, Dewulf, Evelyne M, Pachikian, Barbara D, Neyrinck, Audrey M, Thissen, Jean-Paul, Verrax, Julien, Calderon, Pedro Buc, Pot, Bruno, Grangette, Corinne, Cani, Patrice D, Scott, Karen P, Delzenne, Nathalie M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.06.2012; Public Library of Science (PLoS)
• Subjects: Abl protein; Acids; Acute Disease; Adenoviruses; Animals; Anorexia; Atrophy; Autophagy; Bacteria; BCR protein; Biology; Body fat; Cancer; Cathepsin L; Cathepsins; Cells, Cultured; Chemokines; Colony-stimulating factor; Cytokines; Dendritic cells; Dietary Supplements; Disease Models, Animal; Dysbacteriosis; Ectopic expression; Female; Fusion protein; Fusion Proteins, bcr-abl - genetics; Gastrointestinal Tract - microbiology; Gel electrophoresis; Granulocyte colony-stimulating factor; Homeostasis; Immunity; Inflammation; Inflammation - etiology; Inflammation - prevention & control; Inflammation Mediators - metabolism; Interleukin; Interleukin 4; Interleukin 6; Interleukins; Intestinal microflora; Laboratory animals; Lactobacilli; Lactobacillus - physiology; Leukemia; Leukemia, Experimental - complications; Leukemia, Experimental - genetics; Leukemia, Experimental - pathology; Leukocytes (granulocytic); Liver Neoplasms - metabolism; Liver Neoplasms - microbiology; Liver Neoplasms - pathology; Liver transplants; Markers; Medicine; Metabolism; Metagenome; Mice; Mice, Inbred BALB C; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Multiplexing; Muscles; Muscular Atrophy - etiology; Muscular Atrophy - prevention & control; Musculoskeletal system; Nutrition research; Permeability; Physiology; Precursor Cells, B-Lymphoid - transplantation; Restoration; rRNA 16S; Splenic Neoplasms - metabolism; Splenic Neoplasms - microbiology; Splenic Neoplasms - pathology; Toxicology; Transplantation; Tumor necrosis factor-TNF; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0037971

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.