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bioRxiv · 10.1101/2025.05.27.656368

The Spinal Cord-Gut Axis Regulates Gut Microbial Homeostasis: Insights from a New Murine Metagenomic Catalog

Mohssen, M.·Zayed, A. A.·Kigerl, K.·Du, J.·Smith, G. J.·Schwab, J. M.·Sullivan, M. B.·Popovich, P. G.
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Abstract

The spinal cord, a nexus for brain-body crosstalk, controls gut physiology and microbial homeostasis, but the underlying mechanisms remain unclear. Using genome-resolved longitudinal metagenomics in male and female C57BL/6 mice before and up to 6 months after disrupting the spinal cord-gut axis, we reconstructed over 6,500 microbial draft genomes. This "Mouse B6 Gut Catalog" improved or doubled species- and strain-level representation in other published catalogs. Impaired spinal cord-gut crosstalk induced persistent, sex-, time- and lesion-specific alterations in community composition, marked by a consistent loss of Lactobacillus johnsonii. Feeding this key bacterium to mice with a clinically relevant spinal cord injury improved host health. Genome-resolved, community-contextualized metabolic profiling revealed that shifts in carbohydrate- mediated microbe-microbe interactions explain the reduction of L. johnsonii. These findings identify carbohydrate metabolism as a keystone mechanism shaping gut microbiota and emphasize that mammalian health and gut ecosystem function depend on a functional spinal cord-gut axis. Additionally, these data improve murine microbiome catalogs and demonstrate that metagenome-informed microbial interventions can improve host health and likely mitigate long-term dysbiosis.

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Mohssen, M., Zayed, A. A., Kigerl, K., Du, J., Smith, G. J., Schwab, J. M., Sullivan, M. B., Popovich, P. G.. 2025-05-28. The Spinal Cord-Gut Axis Regulates Gut Microbial Homeostasis: Insights from a New Murine Metagenomic Catalog. https://doi.org/10.1101/2025.05.27.656368

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