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ARS Home » Midwest Area » Lexington, Kentucky » Forage-animal Production Research » Research » Publications at this Location » Publication #416349
Research Project: The Roles of Forage and Phytochemicals at the Plant-Microbe-Animal Nexus for Sustainable Ruminant

Location: Forage-animal Production Research

Title: Microbial-derived exerkines prevent skeletal muscle atrophy

Author
item VALENTINO, TAYLOR - University Of Kentucky
item BURKE, BENJAMIN - University Of Kentucky
item KANG, GYUMIN - University Of Kentucky
item GOH, JENSEN - University Of Kentucky
item DUNGAN, CORY - University Of Kentucky
item ISMAEEL, AHMED - University Of Kentucky
item MOBLEY, BROOKS - University Of Kentucky
item Flythe, Michael
item WEN, YUAN - University Of Kentucky
item MCCARTHY, JOHN - University Of Kentucky

Submitted to: bioRxiv
Publication Type: Pre-print Publication
Publication Acceptance Date: 6/2/2024
Publication Date: 6/2/2024
Citation: Valentino, T.R., Burke, B.L., Kang, G., Goh, J., Dungan, C.M., Ismaeel, A., Mobley, B.C., Flythe, M.D., Wen, Y., McCarthy, J.J. 2024. Microbial-derived exerkines prevent skeletal muscle atrophy. bioRxiv. https://doi.org/10.1101/2024.05.29.596432.
DOI: https://doi.org/10.1101/2024.05.29.596432

Interpretive Summary: Regular exercise yields a multitude of systemic benefits, many of which may be mediated through the gut microbiome. Here, we report that cecal microbial transplants (CMTs) from exercise-trained vs. sedentary mice have modest benefits in reducing skeletal muscle atrophy using a mouse model of unilaterally hindlimb-immobilization. Direct administration of top microbial-derived exerkines from an exercise-trained gut microbiome preserved muscle function and prevented skeletal muscle atrophy.

Technical Abstract: The present study demonstrates that microbiome transplants from exercised-trained donors are able to ameliorate skeletal muscle disuse atrophy. Moreover, the administration of MDEs from an exercise-trained microbiome was able to reproduce this preservation of skeletal muscle mass along with the maintenance of muscle function. Mice were randomly assigned to one of the following groups: sedentary donor, exercised donor, recipient from edentary donor (SED), or recipient from exercised donor (EXR). During metabolite administration experiments, mice were randomly assigned to receive vehicle (VEH), succinate (SUC), pipecolic acid (PIP), or a combination of both succinate and pipecolic acid (PAS). Donor mice were subjected to 8 weeks of progressive weighted wheel running This work leveraged exercise training to alter the composition and function of the gut microbiome in order to assess the therapeutic efficacy of an exercise-trained microbiome and its associated products. Cecal contents collected from three exercise-trained or sedentary mice were pooled and transferred via oral gavage (200µL per transfer) to three anesthetized EXR and SED recipient mice, respectively. Recipient mice received transfers on three consecutive days, followed by a single transfer per week for the next 4 weeks, resulting in 7 total transfers over the course of 5 weeks. (Fig. 1A). Following the final transfer, mice were unilaterally casted to induce skeletal muscle atrophy for 10 daysThese results demonstrate for the first time that an exercise-trained microbiome and associated metabolites elicit phenotypic effects on adult skeletal muscle corresponding with typical exercise adaptation (i.e., the maintenance of muscle mass during disuse as a result of exercise preconditioning). Further, these findings serve as a proof of concept that some of the benefits of regular exercise are, in part, mediated by the gut microbiome.