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

Laure Bindels, Raphael Beck, Olivier Schakman, Jennifer C Martin, Fabienne de Backer, Florence M Sohet, Evelyne M Dewulf, Barbara D Pachikian, Audrey M Neyrinck, Jean-Paul Thissen, Julien Verrax, Pedro Buc Calderon, Bruno Pot, Corinne Grangette, Patrice D Cani, Karen P Scott, Nathalie Delzenne

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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.
Original languageEnglish
Article numbere37971
Number of pages10
JournalPloS ONE
Volume7
Issue number6
DOIs
Publication statusPublished - 27 Jun 2012

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Bindels, L., Beck, R., Schakman, O., Martin, J. C., de Backer, F., Sohet, F. M., Dewulf, E. M., Pachikian, B. D., Neyrinck, A. M., Thissen, J-P., Verrax, J., Buc Calderon, P., Pot, B., Grangette, C., Cani, P. D., Scott, K. P., & Delzenne, N. (2012). Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model. PloS ONE, 7(6), [e37971]. https://doi.org/10.1371/journal.pone.0037971