A role for the gut microbiome on the health and functioning of many tissues, including the brain, liver, kidney, and adiposity, has been widely reported in the literature. Interestingly, 2019 might be the year that the role of the gut microbiome on skeletal muscle (i.e. the gut-muscle axis) comes into greater focus.
The influence of the gut microbiome on muscle strength
In April, Nay et al. reported that endurance exercise capacity was reduced in mice that do not contain a microbiome (germ-free mice, GFM) when compared with conventionally raised, microbiome-containing mice. This finding suggests that there are microbes in the gut that positively influence aerobic exercise performance.
In June, Scheiman et al. identified a causative role for the gut bacterium Veillonella atypica and its metabolic product, the short-chain fatty acid propionate, on improvements in endurance exercise capacity. In July, Lahiri et al. reported decreased muscle mass and muscle strength in GFM, when compared with conventionally raised mice, a finding that suggests a positive role for microbiome-derived factors on muscle mass and function. One of these factors are bacterially-produced short-chain fatty acids (SCFA), as dietary supplementation with a SCFA mixture increased muscle mass and muscle strength in GFM.
My group has recently contributed to the expanding literature on the gut-muscle axis (Fielding et al. 2019). In contrast to the studies mentioned above, few studies aimed at the gut-muscle axis have been performed in older adult humans. First, we investigated microbiome differences between two groups of older adults (average age, ~76y) that differed in terms of body composition and physical functioning.
High-functioning (HF) older adults had a more favorable body composition, including a higher percentage of lean mass and a decreased percentage of fat mass, and better physical functioning, including muscle strength, when compared with LF. We identified microbiome differences between these 2 groups, including higher levels of family-level Prevotellaceae, genus-level Prevotella and Barnesiella, and the bacterial species Barnesiella intestinihominis in HF, when compared with LF older adults.
While identification of bacteria that are different between high-functioning and low-functioning older adults is an important observation, this does not demonstrate causation. One of the better ways to test causation is by transferring fecal samples from older adults into GFM. With use of this approach, a causative role for the gut microbiome on obesity (Ridaura et al. 2013), immunosenescence (Fransen et al. 2017), and other phenotypes has been reported. We then transplanted fecal samples from HF and LF older adults into germ-free mice and measured body composition and physical function in the human microbiome-containing mice 1 month after transplantation.
First, the bacterial differences that were identified above when comparing HF with LF older adult humans were also different when comparing their respectively colonized mice. Second, muscle strength was higher in HF-colonized than LF-colonized mice, evidence that suggests a causative role for these bacteria on the maintenance of muscle strength in older adults. Interestingly, we did not identify a transplantable effect for the gut microbiome of older adults on body composition or treadmill endurance capacity in HF- and LF-colonized mice (a topic for another day!).
The next steps involve further exploration of the role of the gut microbiome on muscle strength. If these bacteria are truly involved, if we increase muscle strength, we’d expect to see a corresponding increase in their intestinal levels. Similarly, if we increase their levels in the gut, do we see a corresponding increase in muscle strength? If so, by what mechanism(s)?
Dr. Lustgarten also gave a talk at our Ending Age-Related Diseases 2019 conference in New York which relates to the research above as well as discussing biomarkers and optimal health.
Lahiri S, Kim H, Garcia-Perez I, Reza MM, Martin KA, Kundu P, Cox LM, Selkrig J, Posma JM, Zhang H, Padmanabhan P, Moret C, Gulyás B, Blaser MJ, Auwerx J, Holmes E, Nicholson J, Wahli W, Pettersson S. The gut microbiota influences skeletal muscle mass and function in mice. Sci Transl Med. 2019 Jul 24;11(502). pii: eaan5662. doi: 10.1126/scitranslmed.aan5662.
Fielding RA, Reeves AR, Jasuja R, Liu C, Barrett BB, Lustgarten MS. Muscle strength is increased in mice that are colonized with microbiota from high-functioning older adults. Exp Gerontol. 2019 Sep 4:110722. doi: 10.1016/j.exger.2019.110722.
Fransen, F., van Beek, A.A., Borghuis, T., Aidy, S.E., Hugenholtz, F., van der Gaast-de Jongh, C., et al. (2017). Aged Gut Microbiota Contributes to Systemical Inflammaging after Transfer to Germ-Free Mice. Front Immunol 8, 1385. doi: 10.3389/fimmu.2017.01385.
Nay K, Jollet M, Goustard B, Baati N, Vernus B, Pontones M, Lefeuvre-Orfila L, Bendavid C, Rué O, Mariadassou M, Bonnieu A, Ollendorff V, Lepage P, Derbré F, Koechlin-Ramonatxo C. Gut bacteria are critical for optimal muscle function: a potential link with glucose homeostasis. Am J Physiol Endocrinol Metab. 2019 Jul 1;317(1):E158-E171. doi: 10.1152/ajpendo.00521.2018.
Ridaura, V.K., Faith, J.J., Rey, F.E., Cheng, J., Duncan, A.E., Kau, A.L., et al. (2013). Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341(6150), 1241214. doi: 10.1126/science.1241214.
Scheiman J, Luber JM, Chavkin TA, MacDonald T, Tung A, Pham LD, Wibowo MC, Wurth RC, Punthambaker S, Tierney BT, Yang Z, Hattab MW, Avila-Pacheco J, Clish CB, Lessard S, Church GM, Kostic AD. Meta-omics analysis of elite athletes identifies a performance enhancing microbe that functions via lactate metabolism. Nat Med. 2019 Jul;25(7):1104-1109. doi: 10.1038/s41591-019-0485-4.