In Aging Cell, researchers have described how different combinations of gut bacteria impact muscle strength in mice.
Expanding upon a known link
The link between gut bacteria and health is well-documented, and multiple biomarkers have confirmed that a healthy gut leads to health elsewhere [1]. This is not just due to inflammation caused by pathogenic bacteria: previous work in mice without existing gut bacterial populations has found that introducing beneficial bacteria leads to better muscle health [2]. The biochemical links have also also been found; for example, beneficial bacteria create short-chain fatty acids (SCFAs) that were demonstrated to benefit muscle health in mice [3].
Research in this area is ongoing; for example, we reported on a paper on a probiotic derived from breast milk earlier this month. These researchers took a different approach to the subject: using bacteria derived from older people with and without sarcopenia, they sought to push towards an effective clinical therapy that uses gut bacterial populations to alleviate frailty.
People with sarcopenia have different gut bacteria
This experiment recruited 51 people with an average age of 74.5 years, and roughly three-fourths were women. 28 of the participants had sarcopenia, and 23 did not.
Sarcopenia was associated with lower levels of acetic acid and butyric acid; this is unsurprising, as butyrate has been documented to have physical benefits. They also trended towards having less SCFAs, although this finding did not meet statistical significance. A total of 37 metabolites were found to be different between the two groups, particularly purine.
People with sarcopenia also had less of Clostridiales and Lachnospira species while having more Butyricimonas virosa, a species that, despite producing butyric acid, has been found to be pathogenic [4]. An evaluation of 16 known probiotics found that one was related to muscle mass and two more were related to physical performance.
The effects of these bacteria were analyzed in mice. There were four groups used in this experiment: mice that were given gut bacteria from people with sarcopenia, mice given gut bacteria from people without it, mice that had their gut bacteria removed through antibiotics, and a pure control group of unaffected mice.
Two weeks later, the antibiotic-treated mice, as expected, had poorer physical metrics than the control group. Their grip strength, interestingly, was on par with the mice given human non-sarcopenic bacteria; the mice given sarcopenic bacteria fared even worse. However, the mice given non-sarcopenic bacteria had greater twitch force than any of the other groups. There were no significant differences in body weight between the four groups. Force induced by repeated (tetanic) contractions was significantly lower in the mice given sarcopenic bacteria, which, unsurprisingly, had the lowest muscle mass.
The gut health of the mice was also affected. The gut mucus of the mice given sarcopenic bacteria was significantly thinner than that of the ones given non-sarcopenic bacteria. They also had more of the inflammatory biomarker Il-1β.
A probiotic solution
In the next part of their study, the researchers looked into probiotics, specifically Lacticaseibacillus rhamnosus (LR), which is correlated with muscle function, and Faecalibacterium prausnitzii (FP), which is correlated with muscle mass. The researchers also tested a combination of the two (LF). Beginning at 20-21 months of age, mice were given one of these treatments alongside a control group for three months.
Only some muscle sizes were improved by the treatments; the quadriceps and gastrocnemius muscle sizes were improved in all treatment groups, and other muscle sizes were only improved in the FP and LF groups. All of the treatments improved grip strength and both twitch and tetanic forces compared to the control group; however, there were no improvements over the baseline, meaning that these probiotic treatments were found to delay but not reverse sarcopenia. Muscle fiber cross-sections were improved by all three treatments.
Metabolism was also found to be positively affected: multiple proteins related to mitochondrial fusion and fission were upregulated, and biochemical cycles that occur in the mitochondrial matrix were upregulated as well. The LF and FP groups had more NRF1, a protein that encourages the creation of mitochondria. Interestingly, either of the bacteria alone improved the NAD+/NADH ratio, but the combination of the two did not. Additionally, a few gene expressions related to muscle atrophy were by from the treatments, although most were unaffected.
There were also improvements in gut health. The gut barrier was improved by all three treatments, but only the LR and LF groups enjoyed increased immunological biomarkers. LR was found to improve amino acid and lipid metabolism, LR and FP separately were found to improve vitamin metabolism, and FP and LF had fewer metabolic diseases than the control group.
While this study was performed with bacteria taken from humans, it was not performed on humans. While substantial work has been done in this overall area, these particular probiotics need clinical verification to determine if they are in fact valuable for fighting sarcopenia.
Literature
[1] Hou, K., Wu, Z. X., Chen, X. Y., Wang, J. Q., Zhang, D., Xiao, C., … & Li, J. Microbiota in health and diseases., 2022, 7.
[2] Lahiri, S., Kim, H., Garcia-Perez, I., Reza, M. M., Martin, K. A., Kundu, P., … & Pettersson, S. (2019). The gut microbiota influences skeletal muscle mass and function in mice. Science translational medicine, 11(502), eaan5662.
[3] Liu, C., Wong, P. Y., Wang, Q., Wong, H. Y., Huang, T., Cui, C., … & Wong, R. M. Y. (2024). Short‐chain fatty acids enhance muscle mass and function through the activation of mTOR signalling pathways in sarcopenic mice. Journal of Cachexia, Sarcopenia and Muscle, 15(6), 2387-2401.
[4] García-Agudo, L., & Nilsen, E. (2018). Butyricimonas virosa: a rare cause of bacteremia. Anaerobe, 54, 121-123.