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Journal of Zhejiang University SCIENCE B
ISSN 1673-1581(Print), 1862-1783(Online), Monthly
2023 Vol.24 No.4 P.312-325
Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells
Abstract: Spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen’s method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal T cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γδ T cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γδ T cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the “gut-spinal cord-immune” axis may be one of the mechanisms regulating neural repair after SCI.
Key words: Short-chain fatty acids (SCFAs); Spinal cord injury (SCI); Regulatory T cells; IL-17+ γδ T cells; Neuroprotection; Inflammation; Motor function recovery
1广西医科大学第一附属医院脊柱骨科，中国南宁市， 530021
2新乡医学院第三附属医院骨科，中国新乡市，453000
3川北医学院附属第二临床医学院，南充市中心医院骨科，中国南充市，637000
4广西医科大学省部共建再生医学与医学生物资源开发与应用协同创新中心，中国南宁市，530021
5广西医科大学公共卫生学院，中国南宁市，530021
摘要：脊髓损伤可以引起运动、感觉和自主神经功能障碍。肠道微生物组在脊髓损伤中具有重要作用，而短链脂肪酸是微生物群的主要生物活性介质之一。在本研究中，我们探讨了口服外源性短链脂肪酸对脊髓损伤运动功能恢复和组织修复的影响。采用Allen方法建立SD大鼠脊髓损伤模型。脊髓损伤后，动物接受含有150 mmol/L短链脂肪酸混合物的水。治疗21天后，BBB评分升高，步态的规律性指数改善，后肢步宽值下降。脊髓组织炎症浸润减轻，脊髓坏死腔减少，运动神经元和尼氏体数量升高。酶联免疫吸附测定（ELISA）、实时定量聚合酶链反应（qPCR）和免疫组化检测显示脊髓中白细胞介素-10（IL-10）表达升高，IL-17表达降低。短链脂肪酸能促进肠道稳态，诱导肠道T细胞转向抗炎表型，促进调节性T细胞（Treg）分泌IL-10，影响脊髓中的Treg细胞和IL-17+ γδ T细胞。此外，我们观察到脊髓损伤后Treg细胞从肠道迁移到脊髓区域。以上结果证实，短链脂肪酸可调节肠道中的Treg细胞，影响脊髓中Treg和IL-17+ γδ T细胞的平衡，抑制炎症反应，促进脊髓损伤大鼠的运动功能。我们的研究结果表明，肠道、脊髓和免疫细胞之间存在一定的关系，"肠道-脊髓-免疫"轴可能是脊髓损伤后神经修复的调节机制之一。
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DOI:
10.1631/jzus.B2200417
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On-line Access:
2023-04-10
Received:
2022-08-22
Revision Accepted:
2022-12-30
Crosschecked:
2023-04-14