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bioRxiv · 10.1101/2024.12.10.627695

A gut-microbiota-muscle axis that protects against age-related motor decline by regulating mitochondrial fission in C. elegans

Dennis, N.·Vazquez-Prada, M.·Xue, F.·Freeman, L. M.·Karamlegos, A.·Kudzminkaite, B.·Ezcurra, M.
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Abstract

Across diverse taxa, the composition of the microbiota is associated with lifelong host health. A mechanistic understanding of how microbial communities influence host physiology could lead to microbiota-based interventions for lifelong health. Here, we have developed a new host-microbiota model system utilising the model organism C. elegans combined with a defined natural microbiota (DefNatMta) consisting of 11 bacteria isolated from wild C. elegans, to study host-microbiota interactions in a more natural setting. We show that DefNatMta colonises the C. elegans gut, forming a stable and distinct gut microbiota. Using DefNatMta, we find a gut microbiota-muscle axis by which the microbiota affects age-related motility and muscular strength and protects against age-related decline in motor function. The gut microbiota-muscle axis acts by altering metabolism and mitochondrial network dynamics in muscle, and requires dynamin-related protein 1 DRP-1, a regulator of mitochondrial fission to protect against age-related motility decline. Our study demonstrates a gut microbiota-muscle axis and microbiota-mitochondria communication affecting age-related muscle function.

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Dennis, N., Vazquez-Prada, M., Xue, F., Freeman, L. M., Karamlegos, A., Kudzminkaite, B., Ezcurra, M.. 2024-12-13. A gut-microbiota-muscle axis that protects against age-related motor decline by regulating mitochondrial fission in C. elegans. https://doi.org/10.1101/2024.12.10.627695

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