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

The spinal cord, a nexus for brain-body crosstalk, controls gut physiology and microbial homeostasis. Here, >6,500 microbial metagenome-assembled genomes were recovered de novo , from male and female C57BL/6 mice gut metagenomes before and up to 6 months after disrupting the “spinal cord-gut axis”. This “Mouse B6 Gut Catalog” improved or doubled species- and strain-level representation in other published catalogs. Analyses showed that breaking the spinal cord-gut axis caused persistent microbial changes that varied by sex, spinal lesion level, and time. A key bacterium, Lactobacillus johnsonii , was consistently reduced, and feeding this to mice with a clinically relevant spinal cord injury improved host health. Genome-resolved, community-contextualized metabolic profiling showed that spinal-dependent effects on microbe-encoded carbohydrate metabolism explain the reduction of L. johnsonii . These data improve murine microbiome catalogs and emphasize that mammalian health and gut ecosystem function depend on a functional spinal cord-gut axis.