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The gut, microbiome and muscles

We have heard about the gut-brain axis, but what about the gut-muscle axis? And most importantly, how does it work and what conditions does it work in?

A 2017 review investigated the role of the gut microbiome in sarcopenia and whether there is a gut-muscle axis that may be involved in its pathogenesis.1

Primary sarcopenia is prevalent in the elderly population and is an age-related condition with multiple unknown causes. It is exacerbated by acute and chronic illness, endocrine dysfunction, inflammation, inactivity, poor nutrition and an unhealthy lifestyle. Secondary sarcopenia is associated with chronic diseases that lead to inflammation and poor mobility, such as cardiovascular disease, lung disease and arthritis. The condition is associated with poor clinical outcomes such as increased hospital admissions, falls, mobility issues and risk of death. Sarcopenia may overlap with frailty, but they are two distinct conditions.1

Sarcopenia is defined by depletion of muscle mass and a reduction in muscle performance which is a result of anabolic resistance and boosted protein breakdown.1

Physical inactivity and inadequate nutrition are hallmarks of primary sarcopenia and gut microbiota composition is strongly reliant on both. It is well known that the gut environment can influence the health of the host by modulating inflammation, insulin sensitivity, energy production and anabolism.1

Chronic inflammation and insulin resistance have been identified as causes of primary sarcopenia which results in reduced muscle protein synthesis, mitochondrial dysfunction, and changed fat deposition.1

Nutrition and physical activity

Malnutrition is seen alongside sarcopenia in the elderly and this may be due to loss of appetite with ageing and chronic inflammatory conditions causing an increase in energy requirements. Nutritional interventions that promote protein synthesis, counter anabolic resistance and modulate inflammation will protect against muscle cell deterioration. These nutrients include Vitamin D, long-chain fatty acids, antioxidants and protein. The protein requirement in the elderly with sarcopenia is 1.2 to 1.5 grams/kg/day to prevent loss of lean muscle mass.1

Physical exercise is crucial to prevent and treat the condition and multiple clinical trials demonstrate positive effects of exercise in the prevention of sarcopenia. Strength training is considered beneficial as it promotes muscle mitochondrial function and biogenesis, oxygen delivery to muscle and differentiation and proliferation of muscle cells.1

Gut microbiota

Ageing is associated with changes to our gut microbiota with a reduction in species diversity, decrease in the taxa representation that has been shown to support health and an increase in Gram-negative pathogens. These changes may be linked to lifestyle changes, disease and medications.1

Clinical trials have found that gut dysbiosis in the elderly is linked to frailty and disability, and an increase in infections such as Clostridium difficile enterocolitis.1

Research has identified the gut microbiota as being involved in immune function, insulin sensitivity, metabolic balance, and host gene expression through different mediators. Nutrition is known to play a key role as these mediators, synthesised by gut bacteria, are derived from the diet. Furthermore, species diversity is inversely correlated to physical performance in older people.1

There is an acceptance of the gut-brain axis where shifts in microbiota can contribute to psychological and neurological disease. There is a pathophysiological connection between the brain and muscle function. So does a gut-muscle axis exist and does it influence muscle function and performance through mediation of the central nervous system?1

Several nutrients** produced or modified by the gut microbiota may promote anabolism in skeletal muscle cells. The amino acid Tryptophan is substrate for muscle protein anabolism and it can be synthesised by gut bacteria. Folate and Vitamin B12, produced by gut bacteria, prevent hyperhomocysteinemia related oxidative stress and endothelial damage which leads to reduced muscle function.1

However, short chain fatty acids (SCFA) which are mediators of the effect of gut microbiota on skeletal muscle since they enter the systemic circulation and can be absorbed by skeletal muscle, are the most studied. SCFAs are produced from bacterial metabolism of nutrients such as protein, and they influence skeletal muscle mitochondria as well as modulate glucose uptake and metabolism and promote insulin sensitivity. Low levels of SCFA-producing bacteria in the gut are associated with increased chronic inflammation which effects anabolic activity. The SCFA, butyrate, is a regulator of several pathways to do with muscle health and when fed to mice it was found to prevent age-related muscle mass loss.1

The authors concluded that the gut microbiota may be involved in the onset and course of sarcopenia. The elderly are often malnourished and it is known that microbiota require nutrients to support their activities and produce beneficial metabolites. SCFA, Tryptophan, B vitamins and the bacteria that produce them may prove to be important biomarkers of sarcopenia. They recommend dietary changes and nutritional supplementation** to improve gut microbiota in these patients. The link between the gut microbiota and muscle physiology should be a priority of aging nutrition, frailty and sarcopenia research.1

**  For quality nutritional supplements and individualised advice, contact us at True Medicine on 07 5530 1863.

Reference

  1. Ticinesi A, Lauretani F, Milani C, et al. Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia: Is there a gut–muscle axis? Nutrients. 2017;9(12):1-20. doi:10.3390/nu9121303