For centuries, biological organisms have adapted to their surroundings to ensure survival, resulting in a rich tapestry of life. Humans, in particular, have forged intricate symbiotic relationships with environmental microorganisms that are indispensable for our well-being and continued existence. Among these, the microbial communities within the human body are especially noteworthy, as they have co-evolved to establish specialized ecological niches in various bodily sites, including the skin, oral cavity, and, most prominently, the gastrointestinal (GI) system.
Engaging in regular physical activity is a well-established means of bolstering immune function and mitigating the incidence of various metabolic and inflammatory disorders. Emerging research indicates that the gut microbiome plays a pivotal role in mediating the beneficial effects associated with exercise. A sophisticated communication network exists between the gut microbiota and skeletal muscles, influencing metabolic processes and modulating inflammatory responses. However, scientific exploration into the precise interplay between the gut microbiome and skeletal muscle health has, until now, remained relatively limited.
In a recently published investigation within the esteemed journal Scientific Reports, researchers embarked on a quest to pinpoint specific intestinal microbes linked to enhanced locomotor performance and increased muscle strength. The methodology involved first depleting the intestinal flora of nine-month-old mice using antifungal and antibiotic treatments. Subsequently, these mice underwent fecal microbiota transplantation (FMT) using samples from healthy human adults who had not used antibiotics or probiotics recently and were free from GI disorders or chronic illnesses, thereby minimizing genetic variability among the hosts.
The researchers meticulously evaluated the effects of FMT on muscle strength using established tests: the Rotarod and wire suspension assessments. The Rotarod test measured overall muscle strength, motor coordination, and balance, while the wire suspension test specifically gauged forelimb strength. These evaluations were conducted both at baseline, prior to FMT, and three months post-FMT. Additionally, blood, gastrointestinal tract contents, and fecal samples were collected to facilitate further detailed analyses. Key metabolic markers, including blood glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC) levels, were quantified. DNA was extracted from GI tract contents and fecal bacterial genomes for 16S rRNA gene sequencing, enabling the calculation of alpha and beta diversities and the construction of phylogenetic trees. Differential abundances of specific microbial strains between groups were analyzed to identify those contributing to muscle strength.
The investigation revealed varied effects of FMT on muscle strength across the murine subjects. Performance changes in the Rotarod and wire suspension tests over three months allowed for the classification of mice into strengthened, intermediate, and weakened groups. Notably, while blood glucose levels and body weight generally increased in mice over the three-month period, HDL-C levels specifically rose within the muscle-strengthened cohorts. A significant increase in species richness was observed post-FMT, indicating a broader range of microbial species, although species evenness remained consistent. The baseline gut microbiome, predominantly composed of Bacteroidetes and Firmicutes, saw a reduction in their relative abundance following FMT, concomitant with an increase in Verrucomicrobia.
Crucially, the microbial diversity found in GI tract samples was considerably richer than in fecal samples, allowing for a more precise detection of muscle-related microbes. The research team pinpointed nine bacterial species with significantly different abundances between the strengthened and weakened groups in the Rotarod test, with seven of these species being more abundant in the strengthened group. Similarly, nine species exhibited differential abundance in the wire suspension test, with four being enriched in the stronger mice. Remarkably, three specific bacterial species—Lactobacillus johnsonii, Limosilactobacillus reuteri, and Turicibacter sanguinis—were consistently found in higher abundance in the strengthened groups across both tests, demonstrating a linear correlation with improvements in muscle strength. While only L. johnsonii and L. reuteri were functionally validated, the repeated enrichment of T. sanguinis suggests its potential biological significance.
In a subsequent phase of the study, 12-month-old mice, serving as an aging model, were given either L. reuteri (LR), L. johnsonii (LJ), or a combination of both strains, procured from the Gut Microbe Bank (GMB). Mice that received both LR and LJ exhibited substantial improvements in both the Rotarod and wire suspension tests. Furthermore, muscle weight in the LR + LJ group increased by an impressive 157% compared to control animals. Although the overall body weight of these mice decreased, this reduction was coupled with a notable increase in muscle mass. The muscle growth was significantly higher in the co-administered group than in mice receiving individual strains. Molecular analysis of muscle growth markers, including follistatin (FST), an inhibitor of myostatin (which restricts muscle growth), and insulin-like growth factor (IGF)-1, a critical anabolic growth factor, revealed that IGF-1 showed the most substantial increase in the LR + LJ group, while FST increased in the LJ group. The cross-sectional areas of various muscle fibers, such as the gastrocnemius, extensor digitorum longus, and soleus, also significantly expanded across all test groups, with the LR + LJ group showing the most pronounced increase. Additionally, the LR + LJ group displayed significantly lower levels of TG, TC, and LDL-C compared to controls. Regarding inflammatory markers, interleukin-6 levels, which were elevated in the LJ group, were markedly reduced in the LR + LJ group, indicating an anti-inflammatory effect of combined probiotic administration.
Collectively, these compelling findings demonstrate that the synergistic action of L. reuteri and L. johnsonii leads to significant enhancements in muscle strength and performance. The co-administration of these strains yielded the most substantial improvements in muscle mass, strength, and fiber cross-sectional area. Although T. sanguinis was not directly validated in this functional assessment, its consistent enrichment in stronger mice warrants further mechanistic investigation. It is imperative to note that these insights are derived from preclinical mouse models. While they strongly suggest that specific gut microbes can profoundly influence muscle health, direct translation to human populations requires rigorous further research. Future studies must aim to corroborate these findings in human cohorts and thoroughly elucidate the underlying molecular mechanisms, including the production of microbial metabolites and their precise effects on muscle metabolism.