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

脊髓损伤 失调 脊髓 肠道菌群 免疫学 移植 炎症 粪便细菌疗法 医学 生物 微生物群 免疫系统 神经科学 生物信息学 内科学 微生物学 艰难梭菌 抗生素
作者
Deshuang Xi,Pan Liu,Yuqian Feng,Yen-Tung Teng,Yu Liang,Junhong Zhou,Hao Deng,Gaofeng Zeng,Shaohui Zong
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:126: 111212-111212
标识
DOI:10.1016/j.intimp.2023.111212
摘要

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.
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