Post-Weaning Gut Microbiota Colonization Reveals Divergent Recovery of Skeletal Muscle and Peripheral Nerves

Following weaning, mice without a complex gut microbiota (CGM) exhibited impaired development of peripheral nerves and motor targets. This study aimed to determine if introducing a complex gut microbiota after weaning could reverse these developmental changes. To do so, germ-free (GF) mice were colonized with a complex gut microbiota by sharing an environment with conventionally raised mice.

Researchers then examined microbiota composition, peripheral nerve structure and gene expression, skeletal muscle protein makeup, neuromuscular junction organization and circulating metabolites in GF, gnotobiotic OMM12, and CGM mice.

Colonization post-weaning led to a partial restoration of microbial diversity, a compositionally distinct microbial community with reduced alpha diversity and an enrichment of Duncaniella muris strain B8. However, despite this successful colonization, peripheral nerve issues remained, such as axon hypermyelination, transcriptional changes in sciatic nerves, longer nodes of Ranvier, and altered axon-glia interactions.

Meanwhile, skeletal muscle problems were largely resolved, with increased muscle mass, normalized protein profiles, restored metabolic and structural pathways, and decreased neuromuscular junction fragmentation. Presynaptic issues, though, persisted.

These results show that the gut microbiota's role in developmental alterations varies greatly in its ability to be reversed across the neuromuscular system. Post-weaning colonization with a complex gut microbiota facilitated a broad recovery of skeletal muscle but did not restore peripheral nerve abnormalities. These findings pave the way for further research on how the timing of microbial colonization, gut microbiota composition, and microbiota-derived signals affect the reversibility of microbiota-dependent neuromuscular changes.