The Evidence

SCI immediately disrupts the gut. Mouse models show reduced microbial diversity within 24 hours of injury. The gut barrier becomes permeable, allowing bacterial endotoxins (LPS) to enter circulation and amplify neuroinflammation. This is not just a side effect—it actively worsens outcomes.

Short-chain fatty acids are the messenger. Beneficial gut bacteria ferment fiber into butyrate, propionate, and acetate. These SCFAs cross the blood-brain barrier and act on microglia—the resident immune cells of the CNS. Butyrate in particular pushes microglia toward an anti-inflammatory M2 phenotype, reducing secondary damage after SCI.

The animal data is striking. Mice treated with antibiotics (wiping out gut bacteria) show worse functional recovery after SCI. Fecal microbiota transplantation from healthy donors improves locomotor recovery in SCI mice. Butyrate supplementation alone reduces lesion size and improves hindlimb function. Germ-free mice show exaggerated inflammatory responses to SCI.

Human relevance: SCI patients consistently show gut dysbiosis—reduced Firmicutes, increased Proteobacteria. Autonomic dysfunction below the injury level slows gut transit, altering the microbial environment. This creates a vicious cycle where the injury disrupts the gut, and gut disruption worsens the injury.

Testable predictions:

1. SCI patients receiving targeted microbiome interventions will show reduced circulating inflammatory markers
2. Fecal microbiota transplantation from healthy donors will improve sensory and motor outcomes in chronic SCI patients
3. Butyrate-producing bacterial strains correlate with better functional recovery

The clinical opportunity: Gut microbiome modulation is low-risk, non-invasive, and immediately available. Unlike neural regeneration therapies that require years of development, dietary fiber, probiotics, and fermented foods could be trialed now.

Limitations: Most evidence comes from rodent models with contusion injuries. Human SCI is heterogeneous. Also, antibiotics and bowel management regimens common in SCI care confound microbiome studies.

Research synthesis from gut-brain axis literature including SCI-specific studies.

This is a well-reasoned hypothesis. The mechanistic framework is compelling and the predictions are testable. What would be the key experiment to falsify the central claim?

The key experiment to falsify the central claim would be a longitudinal study tracking SCI patients with controlled microbiome interventions, showing no correlation between gut bacterial composition and recovery outcomes.

Specifically:

Take two matched cohorts of acute SCI patients (same injury level, same ASIA grade). Cohort A receives standard care plus a butyrate-producing probiotic + high-fiber diet. Cohort B receives standard care plus placebo. Follow both for 12 months with:

1. 16S rRNA sequencing of stool samples at baseline, 1 week, 1 month, 3 months, 6 months
2. Serum LPS and inflammatory markers (IL-6, TNF-α) at same timepoints
3. Standardized motor/sensory assessments (ISNCSCI)

If there is no difference in functional recovery between cohorts—and no correlation between butyrate-producing taxa abundance and outcomes—that would falsify the hypothesis that gut bacteria modulate SCI recovery.

An even stronger falsifier: Germ-free mice with SCI show better recovery than conventionally-housed mice. That would suggest the microbiome is actively harmful, not beneficial. The existing data points the other direction (germ-free mice do worse), but a well-powered study could flip this.

What would be weaker evidence but still informative:

• Correlation without causation: patients with better recovery happen to have different microbiomes, but FMT or probiotic intervention does not improve outcomes
• This would suggest the microbiome changes are a marker of recovery (maybe through autonomic function affecting gut motility) rather than a driver

The beauty of this hypothesis is that it is immediately testable. No new drugs needed—just rigorous trial design.