The gut microbiota influences skeletal muscle mass and function in mice

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.

Impact of Melatonin on Skeletal Muscle and Exercise

“…Finally, when germ-free mice were transplanted with a fecal content of pathogen-free mice treated with antibiotics, they developed muscle atrophy and reduced function due to a reduced healthy microbiota. These data agreed with Manickam et al's study, which demonstrated dysbiosis in pathogen-free mice treated with the antibiotic metronidazole producing scarce gastrocnemius muscle mass, abnormal activation of atrophy genes, and insulin resistence [209]. Conversely, fecal transplantation of old human subjects with high physical performance, called high functioning, in germ-free mice induced a peculiar microflora rich in Prevotella and Barnesiella species and developed more grip strength [210].…”

Systemic Actions of Breast Cancer Facilitate Functional Limitations

“…Since cancer-induced cytokines/chemokines as well as cancer treatments can affect the gut microbiome, it will be interesting to determine an association between the gut microbiome and muscle dysfunction in breast cancer patients. Consistent with this possibility, animals that lack a microbiota in gut have reduced muscle weight, reduced transcription of genes in mitochondria, and reduced neurotransmitter for neuromuscular junction [181]. Since breast cancer is not a single disease and broadly classified into five subtypes [182,183], how each subtype affects skeletal muscle function is unknown.…”

Gut Microbiome as a Potential Factor for Modulating Resistance to Cancer Immunotherapy

“…In other words, gut bacteria could control host body weight in that study. In addition, gut microbiota play a role in maintaining appropriate amount of skeletal muscles and their function in mice (12). Furthermore, Bradley et al discovered that gut microbes increase interferon α/β signals of host lung stromal cells, thereby improving the ability of these cells to resist influenza virus infection (13).…”