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Sci Transl Med. 2019 Jul 24;11(502). pii: eaan5662. doi: 10.1126/scitranslmed.aan5662.

The gut microbiota influences skeletal muscle mass and function in mice.

Author information

1
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. sven.pettersson@ki.se shawonlahiri@gmail.com.
2
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
3
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
4
Division of Computational and Systems Medicine, Department of Surgery and Cancer, Sir Alexander Fleming Building, Imperial College London, London SW72AZ, UK.
5
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
6
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
7
Singapore Center for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore.
8
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
9
Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
10
Department of Neuroscience and Mental Health, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
11
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
12
Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
13
Medical Service, VA New York Harbor Healthcare System, New York, NY 10010, USA.
14
Australian National Phenome Center, Murdoch University, WA 6150, Australia.
15
INRA ToxAlim Integrative Toxicology and Metabolism UMR1331, Chemin de Tournefeuille, Toulouse Cedex, France.

Abstract

The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes Rapsyn and Lrp4 Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.

PMID:
31341063
DOI:
10.1126/scitranslmed.aan5662
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