Microbes and Muscles: The Science behind the Gut-Muscle Connection

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The human gut is home to trillions of microorganisms that make up the gut microbiota. Recent research has shown that these tiny microbes can have a profound impact on our overall health and well-being, including the health and function of our skeletal muscles. This article will dive into the gut-muscle connection. 

The gut-muscle axis, which refers to the communication between the gut microbiota and the skeletal muscles, is a rapidly growing area of research. Scientists are increasingly interested in understanding how the gut microbiota can affect skeletal muscle function and are exploring potential strategies, such as probiotics, to improve muscle health.

In this article, we will explore the current state of research on the gut-muscle connection and the potential impact of gut microbes on skeletal muscle function. We will examine the key questions that researchers are asking in this field, including whether specific strains of probiotics can enhance muscle mass, strength, and endurance. By shedding light on the complex interplay between the gut microbiota and skeletal muscle, we hope to provide insights into how you can optimize your health and fitness through the power of the gut microbiome.

Gut-Muscle Connection: Gut Microbiota and Skeletal Muscle Function

a diagram of the gut-muscle connection
Source: Journal of Cachexia, Sarcopenia and Muscle 2022

The gut microbiota is increasingly recognized as an important player in the regulation of skeletal muscle function. In fact, studies have shown that gut microbiota plays a crucial role in regulating skeletal muscle mass, strength, and metabolism. (1)

Diet and exercise have been found to significantly affect the gut microbiota composition and function, which in turn can impact skeletal muscle function. For example, diets high in fat and sugar have been associated with alterations in the gut microbiota composition, which can lead to inflammation and oxidative stress in skeletal muscles. On the other hand, exercise has been shown to improve gut microbiota diversity and enhance skeletal muscle health.

The potential mechanisms involved in the muscle-gut relationship are complex and multifaceted. One proposed mechanism is the alteration of bile acid by gut microbiota, which can impact skeletal muscle metabolism and glucose homeostasis. (2) Short-chain fatty acids, which are produced by gut microbes during the fermentation of dietary fibers, have also been found to influence skeletal muscle function by enhancing glucose uptake and insulin sensitivity.

The Gut-Muscle Connection, Bile Acids and Secondary Bile Acids

Bile acids are important for lipid digestion and absorption in the intestine, but they also play a role in skeletal muscle metabolism and function. Recent studies have shown that bile acids can modulate skeletal muscle function through a variety of mechanisms. For example, they can activate the farnesoid X receptor (FXR), which plays a crucial role in glucose and lipid metabolism.

The gut microbiota is known to have a significant impact on bile acid metabolism and associated FXR signaling. In particular, gut microbes are capable of producing secondary bile acids, which can have both beneficial and detrimental effects on skeletal muscle function.

Some studies have shown that secondary bile acids may improve skeletal muscle function by increasing the expression of genes involved in energy metabolism and improving insulin sensitivity. However, other studies have suggested that certain secondary bile acids may impair skeletal muscle function by disrupting mitochondrial function and increasing oxidative stress. (3)

Short Chain Fatty Acids and Amino Acids

a diagram of short chain fatty acids and amino acids
Source: Department of Nutrition Science, Purdue University – Summary of principle effects of butyrate and its potential mechanisms of action in the colon and peripheral tissues; liver, skeletal muscle and adipose tissue.

Short-chain fatty acids (SCFAs) and amino acids are two types of substances that are produced by gut bacteria and can affect skeletal muscle function. SCFAs are created when the bacteria ferment dietary fiber in the gut. They are known to have anti-inflammatory properties, which can be beneficial for skeletal muscle health. Additionally, SCFAs have been shown to improve muscle insulin sensitivity, which can lead to better muscle function and metabolism.

Amino acids are essential building blocks for muscle protein synthesis and repair. The gut microbiota has a vital role in amino acid metabolism, with specific bacterial species producing amino acids that can be used by the body. Amino acid availability can be influenced by diet and exercise, and changes in the gut microbiota can also impact amino acid metabolism and availability.

Research suggests that both SCFAs and amino acids can support skeletal muscle function through various mechanisms. For example, SCFAs can enhance mitochondrial function in skeletal muscle, which can improve muscle metabolism and reduce chronic oxidative stress. Amino acids can directly aid muscle protein synthesis and repair, which can improve muscle function and recovery after exercise.

Gut-Muscle Connection: Probiotics and Skeletal Muscle Mass in Aging

gut muscle connection / a photo of the three lyvecap bottles with weights, displaying a probiotic and it's influence on strength

Age-related sarcopenia, which refers to the loss of skeletal muscle mass and function in older adults, is a significant health concern. Recent studies suggest that the gut microbiota plays a crucial role in skeletal muscle metabolism and function, and changes in the gut microbiota have been associated with age-related skeletal muscle loss. (4) To combat this issue, probiotics have been suggested as a potential intervention.

Numerous studies have investigated the effects of probiotics on skeletal muscle mass and function in aging adults. For example, a 12-week randomized, double-blind, placebo-controlled trial found that older adults who received a multi-strain probiotic supplement demonstrated improved lower limb muscle strength and increased lean body mass. Similar findings have been reported in other studies, indicating that probiotics may be beneficial for skeletal muscle mass and function in aging adults. (5)

The exact mechanisms by which probiotics improve skeletal muscle mass, function, and atrophy in aging are not yet fully understood. However, it is believed that probiotics may alter the gut microbiota and its associated metabolites, such as short-chain fatty acids and amino acids, which may support human skeletal muscle metabolism and function. (6) Probiotics may also help to reduce inflammation, which is a major contributor to age-related sarcopenia.

Gut Microbiota, Exercise, and Muscle Function

gut-muscle connection / a photo of swimmers swimming laps in the pool

The maintenance of skeletal muscle function during endurance exercise is heavily influenced by the gut microbiota. Studies have shown that exercise can alter the composition and diversity of the gut microbiota, as well as the metabolic activity of gut bacteria, which can impact skeletal muscle function.

One example of this impact is the increased production of short-chain fatty acids by gut bacteria during exercise. These fatty acids provide an important energy source for skeletal muscle. Additionally, exercise can enhance muscle protein synthesis and muscle glycogen storage, which are essential for maintaining muscle function.

The gut-muscle axis during exercise is a complex interplay between the gut microbiota, the immune system, and skeletal muscle. The gut microbiota can modulate immune function, which can impact skeletal muscle function. Exercise-induced changes in the gut microbiota have been linked to changes in immune cell populations, which can affect muscle recovery and adaptation to exercise.

Although further research is needed to fully understand the mechanisms involved in the gut-muscle axis during exercise, current evidence suggests that the gut microbiota plays a critical role in skeletal muscle function and adaptation to exercise. Modulating the gut microbiota through diet or probiotic supplementation may enhance the benefits of exercise on skeletal muscle function, particularly in aging populations.

Gut-Muscle Connection: Frequently Asked Questions (FAQs)

What is the gut-muscle axis?

The gut-muscle axis refers to the connection between the gut microbiota and skeletal muscle. The gut microbiota can impact various aspects of muscle function, metabolism, and mass through several mechanisms.

How does the gut microbiota affect skeletal muscle?

The gut microbiota can influence skeletal muscle function and mass by regulating nutrient availability, modulating immune and inflammatory responses, and altering the production of neuroactive molecules and bile acids.

What are secondary bile acids, and how do they relate to the gut microbiota?

Secondary bile acids are produced by the gut microbiota through the modification of primary bile acids from the liver. They play an important role in regulating metabolic and physiological processes such as glucose homeostasis, lipid metabolism, and inflammation.

What is skeletal muscle atrophy, and how does it relate to the gut microbiota?

Skeletal muscle atrophy is the loss of muscle mass and function that happens due to aging, chronic diseases, and physical inactivity. The gut microbiota can worsen skeletal muscle atrophy by increasing chronic inflammation, oxidative stress, and the release of catabolic hormones while decreasing protein synthesis and nutrient availability.

How can the gut microbiota help muscle function and adaptation?

The gut microbiota can benefit muscle function and adaptation by improving nutrient absorption and utilization, decreasing inflammation and oxidative stress, and enhancing the release of anabolic hormones and growth factors. Some probiotics and prebiotics have also been shown to promote muscle mass and strength in aging populations.

How does the gut microbiota influence mitochondrial function and energy metabolism in muscles?

The gut microbiota can affect mitochondrial function and energy metabolism in muscles by modulating the production of bile acids, short-chain fatty acids, and other signaling molecules that regulate mitochondrial biogenesis, oxidative phosphorylation, and glucose uptake. Additionally, the gut microbiota can impact the expression of genes related to energy metabolism and fuel utilization in skeletal muscles.


  1. Giron M, Thomas M, Dardevet D, Chassard C, Savary-Auzeloux I. Gut microbes and muscle function: can probiotics make our muscles stronger? J Cachexia Sarcopenia Muscle. 2022 Jun;13(3):1460-1476. doi: 10.1002/jcsm.12964. Epub 2022 Mar 12. PMID: 35278043; PMCID: PMC9178375.
  2. Li G, Jin B, Fan Z. Mechanisms Involved in Gut Microbiota Regulation of Skeletal Muscle. Oxid Med Cell Longev. 2022 May 18;2022:2151191. doi: 10.1155/2022/2151191. PMID: 35633886; PMCID: PMC9132697.
  3. Yin Y, Guo Q, Zhou X, Duan Y, Yang Y, Gong S, Han M, Liu Y, Yang Z, Chen Q, Li F. Role of brain-gut-muscle axis in human health and energy homeostasis. Front Nutr. 2022 Oct 6;9:947033. doi: 10.3389/fnut.2022.947033. PMID: 36276808; PMCID: PMC9582522.
  4. Liao X, Wu M, Hao Y, Deng H. Exploring the Preventive Effect and Mechanism of Senile Sarcopenia Based on “Gut-Muscle Axis”. Front Bioeng Biotechnol. 2020 Nov 5;8:590869. doi: 10.3389/fbioe.2020.590869. PMID: 33251202; PMCID: PMC7674676.
  5. Prokopidis K, Chambers E, Ni Lochlainn M, Witard OC. Mechanisms Linking the Gut-Muscle Axis With Muscle Protein Metabolism and Anabolic Resistance: Implications for Older Adults at Risk of Sarcopenia. Front Physiol. 2021 Oct 26;12:770455. doi: 10.3389/fphys.2021.770455. PMID: 34764887; PMCID: PMC8576575.
  6. Chen LH, Chang SS, Chang HY, Wu CH, Pan CH, Chang CC, Chan CH, Huang HY. Probiotic supplementation attenuates age-related sarcopenia via the gut-muscle axis in SAMP8 mice. J Cachexia Sarcopenia Muscle. 2022 Feb;13(1):515-531. doi: 10.1002/jcsm.12849. Epub 2021 Nov 11. PMID: 34766473; PMCID: PMC8818665.