Targeting the gut microbiota to promote motor rehabilitation after spinal cord injury: mechanisms, evidence, and translational challenges

Spinal cord injury (SCI) is a devastating central nervous system trauma that frequently results in permanent motor dysfunction. Over the past decade the gut microbiota has emerged as a potentially modifiable contributor to secondary injury and neural repair, giving rise to the concept of the gut-spinal cord axis. In this narrative review we synthesize current understanding of how SCI-associated gut dysbiosis may relate to the recovery of motor function, focusing on immune modulation, microbial metabolites such as short-chain fatty acids and bile acids, and gut-central nervous system signaling. Throughout, we deliberately separate evidence obtained in SCI models or in people with SCI from mechanistic evidence generated in other diseases or experimental systems, because conflating these sources is a recurring source of over-interpretation in this field. We then summarize microbiota-targeted interventions studied in animal models-probiotics and prebiotics, fecal microbiota transplantation (FMT), antibiotics and bacteriophages, and direct supplementation with microbial metabolites-and appraise the small, predominantly observational human literature. Several of these interventions improve locomotor outcomes in rodent SCI models, but, with rare exceptions, the causal chain from a microbial change to a functional improvement has not been demonstrated within a single SCI study, and no randomized controlled trial in people with SCI has used motor function as its primary endpoint. We conclude by dissecting the principal translational barriers-inter-individual variability in microbiota composition, uncertain intervention timing and duration, unresolved safety questions, and the absence of standardized pre-clinical-to-clinical pipelines-and by outlining the study designs and reporting standards required to move this field from association toward causation.