Gut microbiota dysbiosis in spinal cord injuries: immune impairment and therapeutic potential of microbiome modulation.

The gut microbiota plays a fundamental role maintaining homeostasis by regulating neuroglial maturation, immune function, and the production of gut derived metabolites (e.g short chain fatty acids and neurotransmitters), while also preventing pathogen colonization. Disruption of this microbial ecosystem characterized by changes in gut microbiota abundance, decreased production of short chain fatty acids (SCFAs), and more pathobionts is known as gut dysbiosis, which has been linked to progression of a range of pathologies, including both traumatic and non-traumatic spinal cord injuries (SCI). Following SCI, a reduction in beneficial bacterial phylum such as Lachnospiraceae and Firmicutes is commonly observed, leading to decreased SCFA production and altered activation of B and T lymphocytes. These changes contribute to -increased intestinal barrier permeability, dysregulated immunoglobulin A secretion, and an imbalance between inflammatory cytokines and anti-inflammatory cytokines. Such disturbances reflect impaired bidirectional communication between the immune system and the gut microbiota, contributing to disease progression. This review synthesizes current evidence on how gut dysbiosis contributes to immune dysfunction after SCI and highlights emerging research that proposes gut microbiota modulation as a novel, cost-effective, and promising therapeutic strategy. Finally, it discusses the clinical implications of these findings and their translational potential, while identifying key knowledge gaps that should be addressed to facilitate the development of microbiome-targeted interventions aimed at improving neurological recovery and quality of life.