Disruption of the spinal cord-gut axis alters microbial dynamics and carbohydrate cross-feeding in the gut.

Spinal cord-gut communication regulates gut bacteria, yet the underlying mechanisms remain poorly understood. Previous studies relied primarily on gene markers with limited functional analysis or genome-resolved snapshots from small cohorts. Here, we assessed microbiome dynamics via genome-resolved metagenomics on 333 samples from male and female C57BL/6 mice collected before and up to six months after surgical disruption of the spinal cord-gut axis. This resulted in 6,635 microbial draft genomes as a foundation for a new "Mouse B6 Gut Catalog" that significantly expands species and strain representation for this widely used laboratory mouse strain. Sampling revealed that disrupted spinal cord-gut signaling causes persistent, lesion-severity-, sex-, and time-specific shifts in microbial community composition, with consistent depletion of Lactobacillus johnsonii. Feeding purified L. johnsonii to spinal cord-injured mice prevented metabolic defects and systemic inflammation caused by disruption of the spinal cord-gut axis. Analyses using genome-resolved and community-based metabolic profiling indicated altered carbohydrate sharing and utilization of gut microbes, potentially depleting L. johnsonii, providing a genome-inferred mechanism for future hypothesis testing. This study improves murine microbiome catalogs, illustrates how metagenome-informed microbial interventions can provide a mechanistic understanding to improve host health, and underscores the vital role of a healthy spinal cord in regulating gut ecosystem function.