Skeletal muscle-gut axis: emerging mechanisms of sarcopenia for intestinal and extra intestinal diseases

Abstract

In recent years, there has been an increasing interest on muscle wasting, considering the reduction of quality of life and the increase of morbidity and mortality associated. Sarcopenia and cachexia represent two conditions of reduction of muscle mass, sharing several elements involved in their pathogenesis, such as systemic inflammation, impaired muscle protein synthesis, increased muscle apoptosis, mitochondrial dysfunction in skeletal muscle tissue and insulin resistance. These features often characterize cancer, inactivity or denervation, but also inflammatory diseases, such as chronic obstructive pulmonary disease, renal failure, cardiac failure, rheumatoid arthritis, inflammatory bowel disease and aging in general. The gastrointestinal tract and gut microbiota are thought to be deeply associated with muscle function and metabolism, although the exact mechanisms that link gut with skeletal muscle are still not well known. This review summarized the potential pathways linking gut with muscle, in particular in conditions as sarcopenia and cachexia. The main emerging pathways implicated in the skeletal muscle-gut axis are: the myostatin/activin signaling pathway, the IGF1/PI3K/AKT/mTOR signaling pathway, which results suppressed, the NF-kB signaling pathway and the FOXO signaling pathway. Further researches in this field are necessary to better explain the linkage between gut microbiota and muscle wasting and the possible emerging therapies associated.