Gut Bacterium Boosts Muscle Strength in Mice and Humans

Researchers have identified a compelling connection between the presence of the gut bacterium Roseburia inulinivorans and enhanced muscle strength in both mice and humans, though the precise underlying processes remain under investigation. Could Gut Bacteria Replicate Exercise Benefits? Aging brings

Researchers have identified a compelling connection between the presence of the gut bacterium Roseburia inulinivorans and enhanced muscle strength in both mice and humans, though the precise underlying processes remain under investigation.

Could Gut Bacteria Replicate Exercise Benefits?

Aging brings about a progressive loss of muscle mass and power, which significantly contributes to frailty, reduced mobility, and adverse health conditions among the elderly population. While physical activity and proper dietary habits stand as the primary strategies to combat this deterioration, their effectiveness is often limited in individuals who are too weak or medically compromised to engage in regular workouts. Consequently, scientists are actively searching for exercise mimetics—innovative treatments that deliver key advantages of physical exertion without requiring actual muscle engagement. The demand for these alternatives has intensified following the rise of Ozempic and similar GLP-1 receptor agonists, which, despite aiding weight reduction, have been linked to substantial losses in lean muscle mass.

In recent years, studies have revealed that the gut microbiome extends well beyond its role in food breakdown. It generates a wide array of compounds that regulate metabolism, control inflammation levels, and affect the functionality of various tissues across the body, including skeletal muscles. Until now, however, no particular bacterial strain had been directly tied to improvements in muscle strength in either human subjects or animal models.

Spotlight on a Promising Bacterial Strain

To address this important knowledge gap, a collaborative team from the University of Almería, the University of Granada, and Leiden University Medical Center in the Netherlands began their study by collecting fecal samples from two distinct groups: 33 older adults and 90 younger adults. These samples underwent detailed analysis, including sequencing of bacterial DNA, to map out the microbiome profiles. The data were then compared against key indicators of physical capability, such as handgrip strength and peak oxygen uptake (VO₂ peak) during physical activity, which serves as a reliable gauge of cardiovascular endurance.

The investigation zeroed in on the Roseburia genus, which exhibited initial promising links to muscle performance metrics. Researchers narrowed their focus to the species level, examining three variants: R. inulinivorans, R. faecis, and R. intestinalis. Among the older participants, individuals with detectable levels of R. inulinivorans in their gut demonstrated 29% greater handgrip strength than those lacking it, without any notable impact on VO₂ peak. The remaining two species displayed no meaningful ties to handgrip performance.

In the younger cohort, elevated levels of R. inulinivorans correlated positively with both handgrip strength and VO₂ peak. This bacterium, along with R. intestinalis, also showed associations with strength in leg press and bench press exercises. Crucially, the study found no substantial links between Roseburia levels and participants' dietary patterns, including intake of calories, carbohydrates, fats, proteins, or fiber, which helps rule out diet as a potential influencing factor.

To establish a causal relationship beyond mere associations, the team administered live cultures of Roseburia bacteria to mice and assessed changes in their muscle capabilities. The experiment involved 32 male mice, aged 6 weeks, which first received a broad-spectrum antibiotic regimen for two weeks to eliminate their existing gut microbiota. The animals were subsequently divided into four equal groups of eight: a control group given a neutral vehicle, and three treatment groups receiving R. faecis, R. intestinalis, or R. inulinivorans, administered three times weekly over eight weeks.

None of the Roseburia strains enhanced the mice's running endurance to exhaustion, a test of stamina and cardiorespiratory capacity. Strikingly, however, R. inulinivorans led to a 30% boost in forelimb grip strength. This improvement held true even after accounting for variations in lean body mass, indicating it was not merely due to increased overall size. Additionally, mice treated with R. inulinivorans exhibited larger cross-sectional areas in their muscle fibers compared to the control group.

Notably, the treatment with R. inulinivorans altered the composition of the soleus muscle, increasing the proportion of type II (fast-twitch) fibers over type I (slow-twitch) fibers. Fast-twitch fibers are primarily responsible for generating power and strength, whereas slow-twitch fibers support sustained endurance activities. These observations aligned closely with the human data, where muscle strength improved without corresponding gains in endurance.

Unraveling the Underlying Mechanisms

Roseburia species are renowned for producing butyrate, a short-chain fatty acid known for its anti-inflammatory properties and roles in metabolic signaling. Thus, an initial theory posited that R. inulinivorans enhanced muscle function by elevating butyrate concentrations. Yet, measurements of short-chain fatty acids in the mice's cecal contents revealed no notable differences between groups, eliminating butyrate as the primary driver.

Shifting focus, the researchers analyzed amino acid profiles and observed profound changes in mice supplemented with R. inulinivorans: levels of methionine, leucine, isoleucine, alanine, valine, and lysine in the cecum were substantially lower than in controls. At first glance, this seemed counterintuitive—how could reduced amino acid availability promote greater muscle strength?

To probe deeper, comprehensive metabolomics assessments—scanning all detectable small molecules in plasma and skeletal muscle—uncovered that R. inulinivorans triggered far more extensive metabolic alterations than the other Roseburia strains. These included shifts in purine metabolism pathways. Purines are essential components of DNA and RNA, vital for energy production via ATP, and broader metabolic processes.

Although the study meticulously cataloged these metabolic shifts, the exact pathway linking them to muscle enhancement is still speculative. In essence, R. inulinivorans may deplete certain amino acids in the gut, prompting the body to redirect resources preferentially to critical tissues like muscles. Simultaneously, muscles might upregulate purine-related pathways to optimize nucleotide synthesis and energy generation amid amino acid scarcity, thereby improving overall efficiency. Additional studies are essential to substantiate this fascinating proposition.

The researchers also examined R. inulinivorans prevalence across age demographics. In their cohorts, older adults aged 65 and above harbored significantly less of this bacterium than young adults aged 18-25. For broader confirmation, they reviewed a large dataset comprising 3,512 fecal metagenomes from healthy people, where adults aged 18-65 showed modestly higher R. inulinivorans levels than seniors, with no clear differences for the other species. A comprehensive meta-analysis of all available public datasets approached but did not achieve statistical significance for any Roseburia species, yet R. inulinivorans displayed a consistent negative trend with age.

“Our results offer robust proof of a gut-muscle connection, where this specific bacterium actively enhances muscle metabolism and strength,” stated Jonatan Ruiz, a professor in the Department of Physical Education and Sport at the University of Granada and investigator at the Joint University Institute for Sport and Health (iMUDS).