Research ArticleGUT MICROBIOTA

The gut microbiota influences skeletal muscle mass and function in mice

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Science Translational Medicine  24 Jul 2019:
Vol. 11, Issue 502, eaan5662
DOI: 10.1126/scitranslmed.aan5662

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Of microbial metabolites and muscle

Skeletal muscle is important not only for locomotion but also for regulating metabolic function. Lahiri et al. studied the interactions between the gut microbiota and skeletal muscle in mice. They identified genes and signaling pathways involved in the regulation of skeletal muscle mass and function that responded to cues from the gut microbiota. Additional biochemical and functional analysis also revealed the influence of the gut microbiota on the function of neuromuscular junctions. These findings open the door to a better understanding of the role of the gut microbiota in the mechanisms underlying loss of muscle mass.

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.

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