Gut–Spinal Cord Axis in Spinal Cord Injury: Bidirectional Inflammatory Mechanisms and Microbiota-Targeted Therapeutic Strategies

Sep 18, 2025Journal of inflammation research

Two-Way Inflammatory Signals Between Gut and Spinal Cord After Injury and Treatments Targeting Gut Bacteria

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Abstract

Spinal cord injury (SCI) is associated with changes in gut microbiota that may influence neurological outcomes.

Gut microbiota alterations following SCI are characterized by dynamic and bidirectional changes.
Microbiota-derived metabolites may act as key mediators in shaping spinal inflammation.
Gut post-SCI could contribute to inflammation by affecting vagal nerve signaling and immune responses.
Interventions targeting gut microbiota, such as probiotics and fecal microbiota transplantation, may help suppress inflammation.
A multiomics approach highlights the need for cross-system therapeutic strategies in the management of SCI.

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Spinal cord injury (SCI) is a complex neurological disorder characterized not only by localized neuroinflammation but also by systemic immune dysregulation and multiorgan dysfunction. Emerging evidence has identified the gut microbiota as a critical extrinsic regulator of neural homeostasis, giving rise to the concept of the "". This review systematically examines the dynamic and bidirectional alterations in the gut microbial composition following SCI, with a particular emphasis on the role of microbiota-derived metabolites in the gut-spinal cord axis. These metabolites are recognized as key mediators that shape the spinal inflammatory milieu by modulating specific signaling pathways. In addition, the mechanistic basis of the gut-spinal cord axis is further dissected through neural, immune, and metabolic regulatory frameworks, highlighting how gut following SCI contributes to spinal inflammation via the modulation of vagal nerve signaling, immune cell polarization, and metabolic homeostasis. Moreover, the translational potential of microbiota-targeted interventions-such as probiotics and fecal microbiota transplantation (FMT)-is evaluated in terms of their ability to suppress inflammatory amplification and restore the disrupted bidirectional gut-spinal cord feedback loop. By integrating multiomics approaches and adopting a spatiotemporal perspective, this review underscores the importance of cross-system therapeutic strategies in SCI, aiming to provide a theoretical foundation and practical guidance for future precision interventions and translational research.

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