Fecal microbiota transplantation regulates the microbiota-gut-spinal cord axis to promote recovery after spinal cord injury

Spinal cord injury (SCI) is devastating for patients, and currently lacks effective treatments. Dysbiosis commonly occurs after SCI and has significant immunomodulatory effects, but its impact on recovery remains unclear. The current study investigated the effects and mechanisms of fecal microbiota transplantation (FMT) in SCI. FMT was administered in a rat model of SCI and spinal pathology, inflammatory cytokines, and gut microbiome composition were assessed. Flow cytometry identified a source of interleukin (IL)-17 in spinal cord tissues, and carboxyfluorescein succimidyl ester labeling tracked gamma delta T cell migration. In vitro coculture was used to analyze the regulatory mechanisms of gamma delta T cells. Seahorse analysis was used to profile dendritic cell (DC) metabolism. Here we show that FMT improved spinal pathology and dampened post-injury inflammation. It also corrected post-SCI dysbiosis, increasing levels of the beneficial bacterium Akkermansia. The therapeutic effects of FMT were mediated by IL-17 produced by gamma delta T cells. FMT regulated gamma delta T cells via DC-T regulatory cell interaction, and induced metabolic reprogramming in DCs. These findings suggest that FMT represents a promising therapeutic approach for SCI, with potential to target IL-17(+) gamma delta T cells. Elucidating the interconnected pathways between microbiota, immunity, and the spinal cord may facilitate novel treatment strategies.