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On-line Access: 2023-04-10

Received: 2022-08-22

Revision Accepted: 2022-12-30

Crosschecked: 2023-04-14

Cited: 0

Clicked: 975

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Shaohui ZONG

https://orcid.org/0000-0003-0868-6222

Gaofeng ZENG

https://orcid.org/0000-0002-0541-7388

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Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.4 P.312-325

http://doi.org/10.1631/jzus.B2200417


Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells


Author(s):  Pan LIU, Mingfu LIU, Deshuang XI, Yiguang BAI, Ruixin MA, Yaomin MO, Gaofeng ZENG, Shaohui ZONG

Affiliation(s):  Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; more

Corresponding email(s):   xiaohui3008@126.com, fengfeng_388@126.com

Key Words:  Short-chain fatty acids (SCFAs), Spinal cord injury (SCI), Regulatory T cells, IL-17+ γ, δ, T cells, Neuroprotection, Inflammation, Motor function recovery


Pan LIU, Mingfu LIU, Deshuang XI, Yiguang BAI, Ruixin MA, Yaomin MO, Gaofeng ZENG, Shaohui ZONG. Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells[J]. Journal of Zhejiang University Science B, 2023, 24(4): 312-325.

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author="Pan LIU, Mingfu LIU, Deshuang XI, Yiguang BAI, Ruixin MA, Yaomin MO, Gaofeng ZENG, Shaohui ZONG",
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%A Pan LIU
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A1 - Yiguang BAI
A1 - Ruixin MA
A1 - Yaomin MO
A1 - Gaofeng ZENG
A1 - Shaohui ZONG
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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+ γ;δ; 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+ γ;δ; 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.

短链脂肪酸通过调节调节性T细胞和IL-17+ γδ T细胞的平衡来改善脊髓损伤的恢复

刘槃1,2,刘明富1,席德双1,白亦光1,3,马瑞鑫4,莫耀民1,曾高峰5,宗少晖1
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。

关键词:短链脂肪酸;脊髓损伤;调节性T细胞;IL-17+ γδ T细胞;神经保护;炎症;运动功能恢复

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AllenAR, 1911. Surgery of experimental lesion of spinal cord equivalent to crush injury of fracture dislocation of spinal column: a preliminary report. JAMA, LVII(11):878-880.

[2]BassoDM, BeattieMS, BresnahanJC, 1995. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma, 12(1):1-21.

[3]BassoDM, BeattieMS, BresnahanJC, et al., 1996. Mascis evaluation of open field locomotor scores: effects of experience and teamwork on reliability. J Neurotrauma, 13(7):343-359.

[4]BazzocchiG, TurroniS, BulzaminiMC, et al., 2021. Changes in gut microbiota in the acute phase after spinal cord injury correlate with severity of the lesion. Sci Rep, 11:12743.

[5]BenakisC, BreaD, CaballeroS, et al., 2016. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat Med, 22(5):516-523.

[6]BezkorovainyA, 2001. Probiotics: determinants of survival and growth in the gut. Am J Clin Nutr, 73(2):399S-405S.

[7]CerviAL, LukewichMK, LomaxAE, 2014. Neural regulation of gastrointestinal inflammation: role of the sympathetic nervous system. Auton Neurosci, 182:83-88.

[8]DoddW, MotwaniK, SmallC, et al., 2022. Spinal cord injury and neurogenic lower urinary tract dysfunction: what do we know and where are we going? J Mens Health, 18(1):24.

[9]EliI, LernerDP, GhogawalaZ, 2021. Acute traumatic spinal cord injury. Neurol Clin, 39(2):471-488.

[10]FerreiraTM, LeonelAJ, MeloMA, et al., 2012. Oral supplementation of butyrate reduces mucositis and intestinal permeability associated with 5-fluorouracil administration. Lipids, 47(7):669-678.

[11]GungorB, AdiguzelE, GurselI, et al., 2016. Intestinal microbiota in patients with spinal cord injury. PLoS ONE, 11(1):e0145878.

[12]HeJ, ZhaoJ, PengX, et al., 2017. Molecular mechanism of miR-136-5p targeting NF-κB/A20 in the IL-17-mediated inflammatory response after spinal cord injury. Cell Physiol Biochem, 44(3):1224-1241.

[13]HillF, KimCF, GorrieCA, et al., 2011. Interleukin-17 deficiency improves locomotor recovery and tissue sparing after spinal cord contusion injury in mice. Neurosci Lett, 487(3):363-367.

[14]HuangR, LiuP, BaiYG, et al., 2022. Changes in the gut microbiota of osteoporosis patients based on 16S rRNA gene sequencing: a systematic review and meta-analysis. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(12):‍1002-1013.

[15]HuuskonenJ, SuuronenT, NuutinenT, et al., 2004. Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids. Br J Pharmacol, 141(5):874-880.

[16]JingYL, YuY, BaiF, et al., 2021a. Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis. Microbiome, 9:59.

[17]JingYL, BaiF, YuY, 2021b. Spinal cord injury and gut microbiota: a review. Life Sci, 266:118865.

[18]JogiaT, RuitenbergMJ, 2020. Traumatic spinal cord injury and the gut microbiota: current insights and future challenges. Front Immunol, 11:704.

[19]KigerlKA, HallJCE, WangLL, et al., 2016. Gut dysbiosis impairs recovery after spinal cord injury. J Exp Med, 213(12):2603-2620.

[20]KigerlKA, MostacadaK, PopovichPG, 2018. Gut microbiota are disease-modifying factors after traumatic spinal cord injury. Neurotherapeutics, 15(1):60-67.

[21]LaneG, GracelyA, BassisC, et al., 2022. Distinguishing features of the urinary bacterial microbiome in patients with neurogenic lower urinary tract dysfunction. J Urol, 207(3):627-634.

[22]LuYT, LiuHY, YangK, et al., 2022. A comprehensive update: gastrointestinal microflora, gastric cancer and gastric premalignant condition, and intervention by traditional Chinese medicine. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(1):1-18.

[23]LucasS, OmataY, HofmannJ, et al., 2018. Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss. Nat Commun, 9:55.

[24]MattSM, AllenJM, LawsonMA, et al., 2018. Butyrate and dietary soluble fiber improve neuroinflammation associated with aging in mice. Front Immunol, 9:1832.

[25]MichelM, GoldmanM, PeartR, et al., 2021. Spinal cord injury: a review of current management considerations and emerging treatments. J Neurol Sci Res, 2(2):14.

[26]MoriyamaM, NishimuraY, KurebayashiR, et al., 2021. Acetate suppresses lipopolysaccharide-stimulated nitric oxide production in primary rat microglia but not in BV-2 microglia cells. Curr Mol Pharmacol, 14(2):253-260.

[27]NakamuraYK, JanowitzC, MeteaC, et al., 2017. Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine. Sci Rep, 7:11745.

[28]O'ConnorG, JeffreyE, MadormaD, et al., 2018. Investigation of microbiota alterations and intestinal inflammation post-spinal cord injury in rat model. J Neurotrauma, 35(18):2159-2166.

[29]ParkJ, KimM, KangSG, et al., 2015. Short-chain fatty acids induce both effector and regulatory T cells by suppression of histone deacetylases and regulation of the mTOR-S6K pathway. Mucosal Immunol, 8(1):80-93.

[30]ParkJ, GoergenCJ, HogeneschH, et al., 2016. Chronically elevated levels of short-chain fatty acids induce T cell-mediated ureteritis and hydronephrosis. J Immunol, 196(5):2388-2400.

[31]PatnalaR, ArumugamTV, GuptaN, et al., 2017. HDAC inhibitor sodium butyrate-mediated epigenetic regulation enhances neuroprotective function of microglia during ischemic stroke. Mol Neurobiol, 54(8):6391-6411.

[32]RamosMG, BambirraEA, CaraDC, et al., 1997. Oral administration of short-chain fatty acids reduces the intestinal mucositis caused by treatment with Ara-C in mice fed commercial or elemental diets. Nutr Cancer, 28(2):212-217.

[33]RatajczakW, RylA, MizerskiA, et al., 2019. Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs). Acta Biochim Pol, 66(1):1-12.

[34]SilvaYP, BernardiA, FrozzaRL, 2020. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne), 11:25.

[35]StephensonJ, NutmaE, van der ValkP, et al., 2018. Inflammation in CNS neurodegenerative diseases. Immunology, 154(2):204-219.

[36]SunGD, YangSX, CaoGC, et al., 2018. γδ T cells provide the early source of IFN-γ to aggravate lesions in spinal cord injury. J Exp Med, 215(2):521-535.

[37]TateDG, ForchheimerM, RodriguezG, et al., 2016. Risk factors associated with neurogenic bowel complications and dysfunction in spinal cord injury. Arch Phys Med Rehabil, 97(10):1679-1686.

[38]ValidoE, BertoloA, FranklGP, et al., 2022. Systematic review of the changes in the microbiome following spinal cord injury: animal and human evidence. Spinal Cord, 60(4):288-300.

[39]WallaceDJ, SayreNL, PattersonTT, et al., 2019. Spinal cord injury and the human microbiome: beyond the brain-gut axis. Neurosurg Focus, 46(3):E11.

[40]XuP, ZhangF, ChangMM, et al., 2021. Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury. J Neuroinflammation, 18:64.

[41]YuBB, QiuHD, ChengSP, et al., 2021. Profile of gut microbiota in patients with traumatic thoracic spinal cord injury and its clinical implications: a case-control study in a rehabilitation setting. Bioengineered, 12(1):4489-4499.

[42]ZhangJX, XieQS, KongWM, et al., 2020. Short-chain fatty acids oppositely altered expressions and functions of intestinal cytochrome P4503A and P-glycoprotein and affected pharmacokinetics of verapamil following oral administration to rats. J Pharm Pharmacol, 72(3):448-460.

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