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Objective The immunoinflammatory response induced by spinal cord injury is a key factor hindering the recovery of neurological functions. Recent studies have shown that gut microbiota dysbiosis can participate in the immune regulation of the central nervous system through the gut-spinal cord axis. This study aims to explore whether curcumin can exert its protective effect on spinal cord injury by reshaping the gut microbiota and thereby regulating the local Treg/Th17 balance in the spinal cord. Methods Female Sprague-Dawley rats weighing 200‒220 g were randomly assigned into the sham operation group, spinal cord injury group, curcumin group, fecal microbiota transplantation group, fecal microbiota transplantation+ curcumin group, and fecal microbiota transplantation+curcumin+GPR inhibitor group. Neurological function recovery was evaluated based on the Basso-Beattie-Bresnahan motor function score and gait analysis. Histopathological changes in the injured area were observed via hematoxylin-eosin staining, Nissl staining, and Luxol Fast Blue staining. RT-qPCR, ELISA, and Western blotting were employed to quantify the expression levels of key transcription factor forkhead box protein 3 (FOXP3) for Treg cells, anti-inflammatory cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β1, as well as key transcription factor retinoic acid receptor-related orphan receptor gamma t (RORγt) for Th17 cells and pro-inflammatory cytokines IL-17 and IL-6 in the spinal cord of each group. Results Compared with the spinal cord injury group and fecal microbiota transplantation group, the curcumin group and fecal microbiota transplantation+ curcumin group showed the most significant improvement in neurological function, specifically manifested by significant increases in BBB motor function scores and gait coordination, along with a marked reduction in the scope of spinal cord injury. At the molecular level, the two groups showed significantly upregulated gene and protein levels of FOXP3, IL-10, and TGF-β1 and significantly inhibited expression of RORγt, IL-17A, and IL-6 in the spinal cord tissue. This suggests that after curcumin intervention in the gut microbiota, the immune balance shifted toward a Treg-dominated anti-inflammatory state. Notably, the aforementioned beneficial effects of curcumin-modified gut microbiota were reversed after combined use of the GPR inhibitor. Conclusion This study indicates that curcumin can act on the gut microbiota to promote the recovery of motor function after spinal cord injury. Curcumin may exert the effect by activating the GPR signaling pathway, thereby upregulating Treg viability, inhibiting Th17 differentiation, and ultimately correcting the Treg/Th17 imbalance. This provides new experimental evidence and application value for using curcumin and its modified gut microbiota as an adjuvant therapeutic strategy for spinal cord injury.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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