Scientists link gut microbes to stronger muscles and healthier aging

Scientists show that specific gut bacteria can supercharge muscle growth and performance in mice, raising hopes for new probiotic-based therapies to combat age-related muscle decline.

Study: Discovery of intestinal microorganisms that affect the improvement of muscle strength. Image Credit: e-crow / Shutterstock

In a recent study published in the journal Scientific Reports, researchers identified intestinal microbes associated with improved muscle strength. Organisms have adapted to their environments for survival, leading to a remarkable diversity of life. Humans have formed symbiotic relationships with environmental microbes vital to health and survival. The microbes in the human body are particularly notable, as they have evolved to create specialized ecosystems specific to each environment, such as the skin, oral cavity, and gastrointestinal (GI) tract.

Physical activity is a key factor in improving immune function and decreasing the incidence of metabolic and inflammatory diseases. The gut microbiome is implicated in mediating the beneficial effects of exercise. Signals from the gut microbiota form a communication network between skeletal muscles and the gut, regulating metabolic activity and inflammation. However, research on the gut microbiota and skeletal muscles is limited.

About the study

In the present study, researchers aimed to identify microbes associated with improved locomotor performance and muscle strength. First, aged (9-month-old) mice were depleted of intestinal microbiota using antifungals and antibiotics, and fecal microbiota transplantation (FMT) was performed using fecal samples to minimize host genetic variability. Fecal samples were obtained from healthy adults on a regular diet who did not use antibiotics or probiotics within the past six months or have GI disorders or chronic illnesses.

Further, the Rotarod and wire suspension tests were performed to evaluate the impact of FMT on muscle strength. Muscle strength, motor coordination, and balance were examined in the Rotarod test. Forelimb strength was assessed in the wire suspension test. Tests were conducted at baseline (before FMT) and three months post-FMT. In addition, blood, gastrointestinal (GI) tract contents, and fecal samples were collected for further analyses.

Blood glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels were assessed. DNA from GI tract contents or fecal bacterial genomes was extracted, and 16S rRNA gene sequencing analysis was performed. The α and β diversities were calculated, and phylogenetic trees were generated. Moreover, specific microbial strains contributing to muscle strength were identified by analyzing differential abundances between groups.

Findings

The researchers found variable effects of FMT on muscle strength. Changes in rotarod or wire suspension test performance over three months were stratified into strengthened, intermediate, and weakened groups. Further, blood glucose levels and body weight of mice increased after three months. Of note, HDL-C levels increased in muscle-strengthened groups.

Species richness significantly increased post-FMT, but species evenness did not change. This meant that while the number of microbial species increased following FMT, their distribution remained relatively stable. The gut microbiome was mainly composed of Bacteroidetes and Firmicutes at baseline; however, their relative abundance decreased after FMT, while that of Verrucomicrobia increased.

Crucially, microbial diversity was significantly richer in GI tract samples than feces, enabling more sensitive detection of muscle-linked microbes. The team found nine bacterial species had significantly different abundances between strengthened and weakened groups within the rotarod test group, with seven species enriched in the strengthened group. Similarly, nine species were differentially abundant between weakened and strengthened mice in the wire suspension group, with four enriched species in the strengthened group.

Notably, three bacterial species, Lactobacillus johnsonii, Limosilactobacillus reuteri, and Turicibacter sanguinis, were consistently enriched in strengthened groups in both tests and showed a linear correlation with muscle strength improvement. Of these, only L. johnsonii and L. reuteri were validated functionally, but the repeated enrichment of T. sanguinis suggests it may also play a biologically relevant role despite not being directly tested.

Finally, 12-month-old (aging-model) mice were administered L. reuteri (LR) and L. johnsonii (LJ) alone or in combination. The strains were sourced from the Gut Microbe Bank (GMB). Mice that received both LR and LJ showed significant improvements in the rotarod and wire suspension tests.

Muscle weight was also increased by 157% in the LR + LJ group compared to controls. Although body weight decreased, it was accompanied by increased muscle mass. Muscle weight in the LR + LJ group was significantly higher than in the LR or LJ groups alone. Muscle growth-related markers, including follistatin (FST), a myostatin inhibitor that promotes muscle growth, and insulin-like growth factor (IGF)-1, a key anabolic growth factor, were assessed at the messenger RNA (mRNA) level. IGF-1 showed the highest increase in the LR + LJ group, whereas FST increased in the LJ group.

Cross-sectional areas of muscle fibers, such as gastrocnemius, extensor digitorum longus, and soleus, were significantly increased across test groups. However, the LR + LJ group showed the largest increase in cross-sectional area of muscle fibers. Moreover, the LR + LJ group had significantly lower TG, TC, and LDL-C levels than controls. Regarding inflammatory markers, interleukin-6 levels were consistently elevated in the LJ group but were markedly reduced in the LR + LJ group, suggesting an anti-inflammatory effect of co-administration.

Conclusions

Taken together, the findings indicate that L. reuteri and L. johnsonii significantly improve muscle strength and performance. Co-administration of these strains resulted in synergistic effects, leading to the highest muscle mass, strength, and fiber cross-sectional area improvements. Although T. sanguinis was not validated, its consistent enrichment highlights the need for future mechanistic exploration.

Importantly, these findings are based on preclinical mouse models. While they suggest that specific gut microbes may influence muscle health, translation to humans requires further investigation. Future studies must corroborate these findings in human populations and elucidate the underlying molecular mechanisms, including microbial metabolite production and effects on muscle metabolism.

Journal reference:

  • Ahn JS, Kim HM, Han EJ, Hong ST, Chung HJ (2025). Discovery of intestinal microorganisms that affect the improvement of muscle strength. Scientific Reports, 15(1), 30179. DOI: 10.1038/s41598-025-15222-2 https://www.nature.com/articles/s41598-025-15222-2

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