The Gut-Muscle Axis and Prevention of Muscle Loss with Aging

Sarcopenia is an involuntary loss of skeletal muscle mass and strength.  It’s considered a multifactorial disease related to aging, chronic inflammation, insufficient nutrition, physical inactivity, and endocrine system disorders (such as reducing estrogen and androgens).

The definition of sarcopenia was mainly based on the decrease in muscle mass and muscle function⁽¹⁾.

Muscle function is commonly evaluated using handgrip strength, 5-times repeated chair stand test, and 4-meter walking speed⁽²⁾.
 
Grip strength is closely related to lower limb muscle strength and calf muscle cross-sectional area, making this test the golden approach for diagnosis and prognosis prediction⁽²⁾. 

In general, the reduction of muscle mass and strength in sarcopenia is closely related to aging.

Additionally, this systemic skeletal muscle disease increases the risk of falls in the elderly, prolongs the length of hospitalization and costs, and increases morbidity and mortality.

Introduction to Gut Microbiota

The gut microbiota can affect the host’s muscle mass and function by regulating systemic inflammation and immunity, substance and energy metabolism, and insulin sensitivity. To date, over 9.9 million microbial genes have been detected in human feces, including more than 1000 different bacteria, most of which are anaerobes⁽³⁾.

Probiotics are beneficial bacteria (eg, Lactobacillus, Bifidobacterium, Clostridium butyricum, Bacillus subtilis) that are primarily found in our digestive system. Prebiotics are mainly oligosaccharides (a type of carbohydrate chain made up of three to 10 simple sugars) that cannot be digested and absorbed by the host⁽⁴⁾.

They feed other beneficial bacteria, thus promoting their growth and reproduction. The preparation that mixes probiotics and prebiotics are called synbiotics⁽⁵⁾.

Synbiotics combine the benefits of probiotics and prebiotics, and have been widely used in research. Gut microbiota changes with age. Healthy aging is related to changes in the structure of the gut microbiota⁽⁶⁾, and its imbalance has a close relationship with human health and disease. Research demonstrates that supplementing with synbiotics in critically ill patients can shorten the length of stay in the ICU, reduce muscle protein catabolism, and reduce infection complications⁽⁷⁾.

Potential Role of Gut Microbiota in Gut-Muscle Axis

There are several studies that have either directly or indirectly proved a certain relationship between muscle mass and gut microbiota. For example, fecal samples from two groups of older adults (high-functioning & low-functioning groups) were transferred into germ-free mice. Grip strength was significantly increased in the high-functioning group, when compared with the low-functioning mice⁽⁸⁾.

Another study found that a prebiotic increases in grip strength in elderly people over 65 years old.

There was no difference in grip strength before the intervention, but following 13 weeks of prebiotic supplementation, grip strength increased significantly in the experimental group compared to the control group⁽⁸⁾.  

Another interesting study found that compared with a control group, supplementing with a prebiotic (Faecalibacterium prausnitzi) can increase muscle mass by enhanced mitochondrial respiration, reduced inflammation, and improved insulin sensitivity⁽⁹⁾.

Probiotics are closely related to muscle strength and function and muscle mass.

Although there is a limited understanding of probiotics’ mechanism on muscle strength and quality; it is clear that the gut microbiota is linked to muscles through endocrine, energy metabolism, immunity and inflammation.

The potential mechanisms of gut-microbiota will be summarized below and are detailed in the figure below.

Mechanism: Mitochondrial and Energy Metabolism

One of the main causes of sarcopenia is thought to occur from skeletal muscle mitochondrial dysfunction or decline⁽¹⁰⁾. Muscle mitochondria function and content, as well as resting and maximal oxygen consumption, decrease with age⁽¹¹⁾.

In addition, ATP that is needed for muscle protein synthesis decreases⁽¹²⁾. Consequently, maintaining healthy mitochondrial mass has a vital role in combating age-related muscle atrophy and weakness⁽¹³⁾.

The gut microbiota relates to skeletal muscle mitochondria through the production of insulin-like growth factor 1 (IGF-1)⁽¹⁴⁾.

Skeletal muscle of germ-free mice that lacked a gut microbiota was compared to the skeletal muscle of pathogen-free mice with gut microbiota and found muscle atrophy decreased IGF-1, and decreased mitochondrial function in germ-free mice without microbiota. Following transplantation of the microbiota in the gut, they saw significant improvement in muscle atrophy and muscle antioxidant capacity⁽¹⁵⁾.

Research indicates that the vicious cycle of muscle atrophy involves the decline of muscle antioxidant capacity and the gut microbiota may maintain muscles’ normal function in terms of antioxidant capacity and mitochondrial function⁽¹⁶⁾.

Mechanism: Immune and Inflammation

Systemic chronic inflammation is one of the most important factors associated with sarcopenia. Research demonstrates that wild mice and ordinary experimental mice have different gut microbiota. Experimental mice are more susceptible to external invasion, suggesting the difference in gut microbiota may have a regulatory effect on the immune system.

There are obvious changes in the gut microbiota in those with inflammatory bowel disease (IBD), which is an inflammatory disease of the intestinal tract. In patients with IBD, the microbiota that produces butyrate is reduced. Butyrate is a short-chain fatty acid (SCFA) that reduces intestinal inflammation, protects the intestinal barrier, and regulates intestinal homeostasis⁽¹⁷⁾.

Increased intestinal permeability is one of the manifestations of the destruction of intestinal barrier function and a potential pathogenic factor for IBD.

Studies indicate that compared with normal people, IBD patients are more likely to have sarcopenia. The mechanisms triggering sarcopenia in IBD mainly include chronic intestinal inflammation, malabsorption of nutrients, lack of exercise, and imbalance of gut microbiota⁽¹⁸⁾.

Therefore, chronic intestinal inflammation, increased intestinal permeability and malnutrition in patients with IBD may affect skeletal muscle mass, leading to sarcopenia, in which the gut microbiota plays an important role.

Gut Microbiota: The Bridge Between Exercise and Sarcopenia

Nutrition and exercise interventions are the most important countermeasures for sarcopenia. Nutritional supplements currently proven to be useful for sarcopenia are protein, essential amino acids, Vitamin D, bisphosphonates, calcifediol and calcium.

Different types of exercise have different effects on muscles. Aerobic endurance exercise can increase the flexibility of exercise. Still, muscle strength and muscle mass improvement are not obvious and can only be used as an auxiliary exercise method.

Resistance exercise can significantly improve muscle strength and affect muscle function and structure at the same time.

Research indicates different gut microbiota composition in obese mice and healthy animals. Following an exercise intervention, the gut microbiota of the experimental group was similar to the one found in normal mice⁽¹⁹⁾.

It seems that the gut microbiota’s composition drastically changes after a long endurance run such as a half marathon). Exercise can also lead to the increase of muscle mass and function through gut microbiota, thereby reducing the occurrence of sarcopenia.

It’s been shown that a 12 week training block of aerobic exercise increased intestinal Bacteroides, as well as trunk muscle strength and cardiopulmonary function in elderly women⁽²⁰⁾.

 This is due to the following reasons:

• Firstly, exercise increases the blood flow in the guts, strengthens the contraction of abdominal muscles, and accelerates the release of gastrointestinal hormones, effectively speeding up the peristalsis of food and shortening the time to pass though the colon. Therefore, the pH of the colon affects the gut microbiota.
• Secondly, aerobic exercise increases the content of short-chain fatty acids in the feces, which slightly reduces the intestines pH, leading to very suitable conditions for intestinal Bacteroides growth⁽²¹⁾.

Intestinal probiotics can reduce inflammation, prevent diarrhea, and intestinal infections, all of which are favorable for the development of sarcopenia⁽²²⁾.

Mechanism: Nutritional Supplements

Protein supplementation is commonly used for the prevention and treatment of sarcopenia.  Gut microbiota can affect the body’s antioxidant effect, skeletal muscle health, and athletic ability.

Research indicates an increase in the number of microbiota in athletes that received 10 weeks of protein supplementation (a mixture of whey and beef). This bacterium is able to fully decompose protein, increase intestinal protein’s utilization rate, and use urea as a nitrogen source⁽²³⁾.

Additionally, the number of Blautia, Roseburia, and Bifidobacterium longum decreased. Blautia and Roseburia are associated with the production of short-chain fatty acids, which have proven health benefits⁽²⁴⁾.

Many studies have established that intestinal microbiota can produce short-chain fatty acids (SCFAs)⁽²⁴⁾.

In mice treated with antibiotics, gut microbiota, the number of SCFAs, and exercise endurance are all reduced. After adding SCFAs, exercise endurance of mice significantly increases. Therefore, the gut microbiota may affect muscle energy metabolism through these SCFAs⁽²⁵⁾.

Some research indicates that alcohol and dietary fiber can play a role in the gut-muscle axis. A high-fiber diet could lead to better physical function compared with a diet low in fiber⁽²⁶⁾.

Studies also demonstrated lower muscle mass and different gut microbiota (more proteobacteria and fewer Enterococcus faecalis bacteria) in people with a long history of heavy alcohol consumption compared to a control group⁽²⁷⁾.

However, this study only clarified this phenomenon but did not prove the causality.

Summary

Research indicates that the gut microbiota can interact with muscle mass and its function through inflammation, immunity, energy metabolism, and insulin sensitivity, thus affecting the body’s physiological function. Both the diagnostic criteria for sarcopenia and detection methods of intestinal flora are rapidly developing, hence making the research process more convenient and efficient.  

Future research on nutrition and exercise and the gut-muscle axis are needed with a focus on the effects of probiotics, prebiotics, synbiotics, and certain drugs on muscle mass and function, as the gut-muscle axis is a very promising research direction in sarcopenia.

But don't wait on research to keep your gut health and muscle mass in an optimal state.

Supplementing with probiotics and protein are simple things you can do right now to ensure your body has the tools it needs to be healthy and strong.

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