Department of Spine and Osteopathy Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.
Department of Orthopaedics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, He-nan, China.
Int Immunopharmacol. 2024 Jan 5;126:111212. doi: 10.1016/j.intimp.2023.111212. Epub 2023 Nov 17.
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 γδ T cell migration. In vitro coculture was used to analyze the regulatory mechanisms of γδ 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 γδ T cells. FMT regulated γδ 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 γδ T cells. Elucidating the interconnected pathways between microbiota, immunity, and the spinal cord may facilitate novel treatment strategies.
脊髓损伤 (SCI) 对患者来说是毁灭性的，目前缺乏有效的治疗方法。SCI 后常发生菌群失调，并具有显著的免疫调节作用，但对其恢复的影响尚不清楚。本研究探讨了粪便微生物群移植 (FMT) 在 SCI 中的作用和机制。在 SCI 大鼠模型中进行了 FMT，并评估了脊髓病理学、炎症细胞因子和肠道微生物组组成。流式细胞术鉴定了脊髓组织中白细胞介素 (IL)-17 的来源，并用羧基荧光素琥珀酰亚胺酯标记追踪 γδ T 细胞迁移。体外共培养用于分析 γδ T 细胞的调节机制。使用 Seahorse 分析来描绘树突状细胞 (DC) 的代谢情况。本研究表明，FMT 改善了脊髓病理学并减轻了损伤后的炎症。它还纠正了 SCI 后的菌群失调，增加了有益细菌 Akkermansia 的水平。FMT 的治疗效果是通过 γδ T 细胞产生的 IL-17 介导的。FMT 通过 DC-T 调节性细胞相互作用调节 γδ T 细胞，并诱导 DC 代谢重编程。这些发现表明，FMT 是一种有前途的 SCI 治疗方法，有可能靶向 IL-17 γδ T 细胞。阐明微生物群、免疫和脊髓之间的相互关联途径可能有助于开发新的治疗策略。
