Sarcopenia, or the loss of muscle mass, strength and function, is a pressing global health issue affecting roughly 10% of adults by the time they turn 60 and nearly half of adults over the age of 80. The condition is associated with a high risk of falls and fractures, and is estimated to cost the UK £2.5 billion annually. In the U.S., this figure rises to $40 billion.
While several factors underpin the development of sarcopenia, including lack of physical exercise, a low protein diet, chronic inflammation and insulin resistance, researchers have now begun to explore the role of age-associated changes in gut microbiome composition and sarcopenia progression.
In a new paper, published in Ageing Research Reviews, researchers from Birmingham Biomedical Research Centre in the UK identified a number of biological factors present in older age which may influence muscle wastage. In the gut, this includes short-chain fatty acid (SCFA) and bile acid production and gut barrier integrity.
“Age-related changes in the gut microbiome, characterized by reduced diversity and altered metabolite production, may compromise intestinal barrier function, leading to increased permeability,” they wrote. “These age-associated changes in the gut microbiome led to changes in circulating microbial metabolites and toxins, such as a decrease in short-chain fatty acids, an increase in lipopolysaccharides and an imbalance in bile acid production. Together these alterations may contribute to the development of sarcopenia through impairments in muscle protein turnover.”
The study explored whether lifestyle-based approaches, such as exercise, diet and pre, pro and postbiotics may be able to target the gut muscle axis, thereby lowering the risk of sarcopenia. It also evaluated newer strategies such as urolithin A and fecal microbiome transplants (FMT) to assess whether these novel approaches could help manage sarcopenia.
Can exercise reshape the aging gut microbiome?
During adult life, the composition of the gut microbiome remains relatively stable. However, in older age, it starts to change. Typically, this is characterized by a decline in microbial diversity, including a decrease in SCFA producers and an increase in Proteobacteria phylum, which can cause disease when overabundant.
These alterations have been linked to physiological changes such as chronic low-grade inflammation (often referred to as ‘inflammaging’), impaired gut barrier function (leaky gut) and reduced metabolic function, all of which are implicated in the development of sarcopenia.
However, relatively few human studies have explored the relationship between the gut-microbiome and sarcopenia. Of the existing evidence, the researchers found that SCFA production, bile acid production and intestinal barrier leakage may all impact muscle protein synthesis in older age. Methods that increase SCFA and bile production, while strengthening the gut barrier, may therefore help prevent the onset of age-related muscle loss.
Exercise is known to be a critical component in targeted strategies to improve muscle mass and function in older populations, and it is now being explored as a method to induce alterations in gut microbiome composition.
In one study published in Physiological Reports, the researchers tested whether five weeks of aerobic exercise affected gut microbiome composition in older men. The results revealed an increase in the relative abundance of Oscillospira (a SCFA producer) and a decrease in Clostridium difficile (a pathogenic bacterium that can cause severe inflammation).
Another study that analyzed the effects of various exercise programs in healthy older women found that aerobic exercise led to a relative increase in intestinal Bacteroides, which was associated with improvements in a six-minute walking test.
However, the authors of the review stated that no studies have identified a positive impact on the gut microbiota following resistance exercise only, suggesting that modulation of the gut microbiome is specific to exercise modality.
Silvia Barbaresi, a microbiologist and sport scientist, and chief scientific officer at Italy-based start-up Minutia.AI, noted that this disconnect reflects different biological adaptations to training stimuli.
“The gut microbiome appears to be more tightly linked to metabolic and energetic adaptations (endurance physiology) than to mechanical hypertrophy signaling (muscle growth),” she said. “Aerobic training induces widespread metabolic changes—including enhanced mitochondrial biogenesis, increased fatty-acid oxidation, improved lactate turnover and greater overall energy flux—that alter substrate availability and circulating metabolites, thereby exerting strong ecological pressure on gut microbial communities.
“In contrast, resistance exercise primarily promotes muscle growth through localized mechanical and anabolic signaling pathways, particularly the mTOR signaling pathway, which depends more on mechanical load and amino-acid availability than on systemic metabolic shifts.”
This, according to Barbaresi, suggests that while resistance training remains the most effective stimulus for increasing muscle mass and strength, aerobic exercise appears to exert a stronger influence on gut microbial composition, highlighting the microbiome’s potential role in regulating endurance capacity and metabolic flexibility.
The potential of pre, pro and postbiotics for muscle health
Biotics have emerged as a promising tool to impact muscle protein synthesis by promoting microbial diversity, with one recent meta-analysis of 17 probiotic supplementation studies identifying beneficial effects on muscle mass, strength and function.
Saki Yamashita, marketing manager of global probiotics manufacturer Morinaga, said that it is unlikely that probiotics directly increase the size of muscle cells or tissues (hypertrophy) but may work by inhibiting muscle breakdown.
“There is no published human data from Morinaga showing direct stimulation of muscle protein synthesis,” she said. “However, our preclinical data shows the increased soleus muscle mass and altered fiber composition toward oxidative profiles—suggesting indirect anabolic or anti‑catabolic modulation, not classic hypertrophy.”
Positive results have been seen across multiple species and strains. For example, B. breve has been shown to strengthen epithelial barrier function, upregulate mucin and tight‑junction proteins, and suppress inflammatory taxa, according to Morinaga’s research. In animal models, this species has also been shown to reduce low-grade inflammation and improve adiponectin signaling, Yamashita added.
Given that probiotics may be able to induce such effects, researchers have hypothesized that prebiotics and postbiotics may also prevent muscle wastage via the gut-muscle axis. While human research involving postbiotics is limited, pre-clinical models suggest SCFAs, such as butyrate, may increase muscle fiber cross-sectional area, attenuate age-related declines in muscle mass and reduce fatty tissue.
Prebiotics, on the other hand, have been assessed in the context of frailty in a number of clinical trials. In one study published in the International Journal of Molecular Science, frail adults over the age of 65 were given Darmocare Pre, a prebiotic supplied by Netherlands-based prebiotic company Bonusan, which contains inulin and fructooligosaccharides (FOS). Findings indicated improvements in levels of exhaustion and handgrip strength (components associated with frailty), but no significant influence on overall frailty scores was identified.
A similar study published in Nature Communications resulted in an increase in Bifidobacteria and improvement in cognitive function, but not in improved muscle strength as measured by chair rise time. This suggests that further research is needed to determine the impact of prebiotic supplementation on muscle mass and strength.
“To promote muscle growth, several stimuli are required, including a physical stimulus in the form of exercise, the presence of sufficient anabolic endocrine factors such as IGF-1, mTOR signaling and the availability of adequate protein intake,” said Fien Demeulemeester, head of science and education at Bonusan, who noted that anabolic resistance (the reduced ability of aging muscle to respond to stimuli like protein intake and exercise) is common in older age.
“Taking FOS alongside exercise (either pre- or post-workout) is not expected to make a major difference, as this intervention targets gut health and the gut–muscle axis rather than directly influencing anabolic processes in the way protein or amino acids do. [However], FOS is able to facilitate changes in the microbiome which could ameliorate anabolic resistance.”
Novel and emerging methods
In their review, the researchers from Birmingham Biomedical Research Centre noted that while modifying the microbiome through exercise and biotics may prove helpful in sarcopenia management, there is not enough evidence to conclusively support their use.
They did however highlight other promising approaches including supplementation with urolithin A. This naturally occurring gut metabolite, which is produced by eating foods such as pomegranates, nuts and berries, is experiencing rapid growth in the supplement market, primarily due to its ability to induce mitophagy.
Swiss life sciences company Timeline has pioneered much of the research on this compound with its patented urolithin A ingredient, marketed as Mitopure.
“Around 60% to 70% of adults cannot produce meaningful urolithin A from diet alone, and even those who can tend to have levels too low to be of real benefit,” said Dr. Anurag Singh, chief medical officer at Timeline. “Supplementing with Mitopure, […] stimulates mitochondrial renewal and restores cellular energy efficiency in muscle and other key organs. In placebo-controlled trials, Mitopure supplementation significantly increased mitochondrial renewal and improved muscle strength by 12% in healthy middle-aged adults without any changes to diet or exercise.”
Pre-clinical research suggests urolithin A stimulates muscle strength by acting as a mitophagy activator, which improves mitochondrial health and energy metabolism within muscle cells, presenting a promising tool for age-related muscle decline. This presents opportunities to reach a wide audience of health-aware consumers, according to Federico Luna, Timeline’s chief marketing officer.
“Primary consumers are both health strivers that take a pro-active and preventive approach to healthy aging and older adults where muscle decline is a common problem to prevent future frailty and sarcopenia conditions,” he said. “Consumers are increasingly aware that age-related muscle decline is a priority and the decline starts much sooner than most people think.”
Finally, the review authors highlighted Fecal Microbiota Transplantation (FMT) as a potential therapeutic strategy for muscle wastage. One animal study reported that older rats which received FMT from younger rats exhibited better maintenance of the intestinal barrier, along with reduced age-related declines in muscle mass, strength and physical function.
FMT, however, has not yet been tested as a treatment for sarcopenia in humans. Furthermore, research from the Institute for Systems Biology (ISB) in Seattle suggests that natural, age-related changes to the gut microbiota are sometimes protective, rather than a sign of declining health.
Investigations by Sean Gibbons, a microbiome researcher and associate professor at ISB, show that healthy older people have more distinct gut microbiomes compared to less healthy older adults. In fact, less healthy older people tended to maintain core microbes that were dominant in their younger years, with those in the lowest tertile of ‘uniqueness’ more likely to die over a four-year follow-up period.
“If you’re 80, you probably don’t want a 20-year-old microbiome–this might not be good for you,” he said during a presentation at the IPA World Congress + Probiota 2025. “You probably want a gut microbiome that’s adapted to the physiology of your 80-year-old body. [For this reason], I would suggest that people do not give FMTs from 20-year-olds to 80-year-olds […] it’s too early and there’s not enough evidence for that.”
