Traumatic brain injury (TBI) triggers a cascade of neurological impairment, cerebrovascular dysfunction, and gut microbiota dysbiosis, perpetuating a cycle of neuroinflammation. Exercise is known to promote recovery, however; its impact on the integrated gut-brain axis following TBI remains unexplored. In this study, we investigated the capacity of voluntary exercise to reverse TBI-induced cerebral hypoperfusion and gut dysbiosis. Male Kunming mice were randomly assigned to sham or TBI groups, with or without access to voluntary exercise for 7 days, starting 48 h post-injury. We assessed neurological deficits, cerebral blood flow (CBF), and gut microbiota composition. Results showed that voluntary exercise facilitated neurological recovery, restoring motor coordination and balance by day 7. It reversed 90.1% of the acute cerebral perfusion deficit and fully restored interhemispheric symmetry. TBI-induced gut dysbiosis was counteracted, as evidenced by rescued alpha diversity, normalized beta diversity, and profound taxonomic shifts that suppressed pro-inflammatory pathobionts and enriched immunomodulatory commensals. These findings suggest that voluntary exercise serves as a multisystem therapy for TBI by facilitating neurological recovery, normalizing cerebrovascular perfusion, and restoring gut microbiota homeostasis.
