Research Progress on the Effect and Mechanism of Probiotics in Relieving Parkinson's Disease Related Symptoms
-
摘要: 帕金森病（Parkinson’s disease，PD）是一种常见的脑部神经病变。近年来，越来越多的证据表明肠道菌群失调与PD的发生发展密切相关。由此提示，从肠道微生物角度出发，可能是治疗PD的新策略。益生菌是一类能够定植于宿主肠道并对机体健康发挥有益作用的活性微生物，对维持肠道微生态平衡具有重要的意义。研究表明，益生菌可通过肠-脑轴有效预防和改善PD，潜在的作用机制包括调节肠道微生态，减轻炎症反应和氧化应激损伤，促进神经营养因子的表达等。本文综述了肠道菌群在PD中的变化，肠道菌群在PD发病中的机制，益生菌对PD相关症状的改善作用及机制等，以期为益生菌预防和缓解PD提供理论基础。Abstract: Parkinson's disease (PD) is a common neurological disorder of the brain. In recent years, there is increasing evidence that intestinal flora dysbiosis is closely related to the occurrence and development of PD. This suggests that intestinal microorganisms may be a new strategy for the treatment of PD. Probiotics are a group of active microorganisms that can colonize the host gut and play a beneficial role in the health of the body, and are of great significance to maintaining the intestinal microecological balance. Studies have shown that probiotics can effectively prevent and improve PD through the gut-brain axis, and the potential mechanisms of action include regulating intestinal microecology, alleviating inflammatory response and oxidative stress damage, and promoting the expression of neurotrophic factors. This article reviews the changes of intestinal flora in PD, the mechanisms of intestinal flora in the pathogenesis of PD, and the improvement effect and mechanisms of probiotics on PD-related symptoms, in order to provide a theoretical basis for probiotics to prevent and alleviate PD.
-
Key words:
- Parkinson's disease /
- probiotics /
- gut microbiota /
- mechanism
-
表 1 PD患者肠道菌群变化
Table 1. Changes in intestinal flora in patients with PD
受试群体 检测技术 数量降低的
肠道菌群数量增加的
肠道菌群参考文献 80例PD患者病和72例健康者 16S rRNA
基因测序毛螺菌科 乳酸杆菌科、
肠杆菌科、
肠球菌科[29] 64例PD患者和64例健康者 16S rRNA
基因测序普雷沃氏菌科、
毛螺菌科、
紫红球菌科、
罗氏菌属双歧杆菌科、
理研菌科[30] 80例PD患者和77例健康者 16S rRNA
基因测序普雷沃氏菌属 疣微菌门、
Mucispirillum、
Parabacteroides、
卟啉菌属、
乳酸杆菌属[31] 197例PD患者和103例健康者 16S rDNA 毛螺菌科、
罗氏菌属、
粪杆菌属Christensenellacea、
双歧杆菌属、
柯林斯菌属、Bilophil、阿克曼菌属[32] 64例PD患者和51例健康者 16S rRNA
基因测序拟杆菌属、
布劳特氏菌属、
毛螺菌科、
丁酸梭菌属、
罗氏菌属阿克曼菌属、
埃希氏菌属、
双歧杆菌属、
链球菌属[33] 193例PD患者和113例健康者 16S rRNA
基因测序毛螺菌科、
罗氏菌属、变形菌门、
肠杆菌科、
Christensenellacea、
乳酸杆菌科、
双歧杆菌科、
Parabacteroides[34] 34例PD患者和34例健康者 qPCR法 乳酸杆菌科、
粪杆菌属、
普雷沃氏菌科肠杆菌科、
双歧杆菌属、[35] 
下载: 导出CSV
表 2 不同益生菌对PD的作用
Table 2. The role of different probiotics on PD
菌种名称 受试对象 剂量 周期 研究结果 参考文献 嗜酸乳杆菌+婴儿双歧杆菌 人 60 mg（每日两次） 3个月 改善腹痛和腹胀 [42] 嗜酸乳杆菌+两歧双歧杆菌+罗伊氏
乳杆菌+发酵乳杆菌人 8×109 CFU/d 12周 降低MDS-UPDRS评分、超敏C反应蛋白和MDA水平，
提高GSH水平[43] 嗜酸乳杆菌等多菌株益生菌胶囊 人 1010 CFU/d 4周 改善便秘症状，增加排便次数 [40] 乳酸菌+双歧杆菌+低聚果糖 人 3×1010 CFU（每日两次） 8周 增加排便频率，缩短肠道传输时间 [39] 多菌株益生菌+益生元纤维 人 2.5×1011 CFU/d 4周 增加完整排便频率 [41] 两歧双歧杆菌等多菌株益生菌 小鼠 1010 CFU/d 16周 改善平衡、协调和步态功能障碍，保护多巴胺能神经元 [44] 短双歧杆菌 小鼠 1×109 CFU/d 4 d 减少场景恐惧记忆的遗忘，改善认知功能 [45] 嗜酸乳杆菌+两歧双歧杆菌+罗伊氏
乳杆菌+发酵乳杆菌大鼠 8×109 CFU/d 14 d 减少旋转行为，改善认知功能，减少脂质过氧化和
神经元损伤[46]
下载: 导出CSV
-
[1] VIJIARATNAM N, SIMUNI T, BANDMANN O, et al. Progress towards therapies for disease modification in Parkinson's disease[J]. Lancet Neurology,2021,20(7):559−572. doi: 10.1016/S1474-4422(21)00061-2 [2] LI G, MA J, CUI S, et al. Parkinson's disease in China: A forty-year growing track of bedside work[J]. Transl Neurodegener,2019,8:22. doi: 10.1186/s40035-019-0162-z [3] AARSLAND D, BATZU L, HALLIDAY G M, et al. Parkinson disease-associated cognitive impairment[J]. Nat Rev Dis Primers,2021,7(1):47. doi: 10.1038/s41572-021-00280-3 [4] TOLLESON C M, FANG J Y. Advances in the mechanisms of Parkinson's disease[J]. Discovery Medicine,2013,15(80):61−66. [5] ZHENG S Y, LI H X, XU R C, et al. Potential roles of gut microbiota and microbial metabolites in Parkinson's disease[J]. Ageing Research Reviews,2021,69:101347. doi: 10.1016/j.arr.2021.101347 [6] RUTSCH A, KANTSJÖ J B, RONCHI F. The gut-brain axis: How microbiota and host inflammasome influence brain physiology and pathology[J]. Front Immunol,2020,11:604179. doi: 10.3389/fimmu.2020.604179 [7] KIM S, KWON S H, KAM T I, et al. Transneuronal propagation of pathologic α-synuclein from the gut to the brain models Parkinson's disease[J]. Neuron,2019,103(4):627−641. doi: 10.1016/j.neuron.2019.05.035 [8] RANI L, MONDAL A C. Unravelling the role of gut microbiota in Parkinson's disease progression: Pathogenic and therapeutic implications[J]. Neuroscience Research,2021,168:100−112. doi: 10.1016/j.neures.2021.01.001 [9] SHEN T, YUE Y, HE T, et al. The association between the gut microbiota and Parkinson's disease, a meta-analysis[J]. Front Aging Neurosci,2021,13:636545. doi: 10.3389/fnagi.2021.636545 [10] AZAD M A K, SARKER M, LI T, et al. Probiotic species in the modulation of gut microbiota: An overview[J]. Biomed Res Int,2018,2018:9478630. [11] KIOUSI D E, KOUROUTZIDOU A Z, NEANIDIS K, et al. Evaluating the role of probiotics in the prevention and management of age-related diseases[J]. International Journal of Molecular Sciences,2022,23(7):3628. doi: 10.3390/ijms23073628 [12] SNIGDHA S, HA K, TSAI P, et al. Probiotics: Potential novel therapeutics for microbiota-gut-brain axis dysfunction across gender and lifespan[J]. Pharmacol Ther,2022,231:107978. doi: 10.1016/j.pharmthera.2021.107978 [13] MIRZAEI H, SEDIGHI S, KOUCHAKI E, et al. Probiotics and the treatment of Parkinson's disease: An update[J]. Cellular and Molecular Neurobiology,2022,42(8):2449−2457. doi: 10.1007/s10571-021-01128-w [14] DOROSZKIEWICZ J, GROBLEWSKA M, MROCZKO B. The role of gut microbiota and gut-brain interplay in selected diseases of the central nervous system[J]. International Journal of Molecular Sciences,2021,22(18):10028. doi: 10.3390/ijms221810028 [15] SUN P, SU L, ZHU H, et al. Gut microbiota regulation and their implication in the development of neurodegenerative disease[J]. Microorganisms,2021,9(11):2281. doi: 10.3390/microorganisms9112281 [16] BULLICH C, KESHAVARZIAN A, GARSSEN J, et al. Gut vibes in Parkinson's disease: The microbiota-gut-brain axis[J]. Mov Disord Clin Pract,2019,6(8):639−651. doi: 10.1002/mdc3.12840 [17] SCHEPERJANS F, AHO V, PEREIRA P A, et al. Gut microbiota are related to Parkinson's disease and clinical phenotype[J]. Movement Disorders,2015,30(3):350−358. doi: 10.1002/mds.26069 [18] MINATO T, MAEDA T, FUJISAWA Y, et al. Progression of Parkinson's disease is associated with gut dysbiosis: Two-year follow-up study[J]. PLoS One,2017,12(11):e0187307. doi: 10.1371/journal.pone.0187307 [19] HUANG Y, LIAO J, LIU X, et al. Review: The role of intestinal dysbiosis in Parkinson's disease[J]. Front Cell Infect Microbiol,2021,11:615075. doi: 10.3389/fcimb.2021.615075 [20] ZHAO J, BI W, XIAO S, et al. Neuroinflammation induced by lipopolysaccharide causes cognitive impairment in mice[J]. Sci Rep,2019,9(1):5790. doi: 10.1038/s41598-019-42286-8 [21] WALLEN Z D, APPAH M, DEAN M N, et al. Characterizing dysbiosis of gut microbiome in PD: Evidence for overabundance of opportunistic pathogens[J]. NPJ Parkinsons Dis,2020,6:11. doi: 10.1038/s41531-020-0112-6 [22] SAMPSON T R, DEBELIUS J W, THRON T, et al. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease[J]. Cell,2016,167(6):1469−1480. doi: 10.1016/j.cell.2016.11.018 [23] SUN M F, ZHU Y L, ZHOU Z L, et al. Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway[J]. Brain Behav Immun,2018,70:48−60. doi: 10.1016/j.bbi.2018.02.005 [24] ZHAO Z, NING J, BAO X Q, et al. Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis[J]. Microbiome,2021,9(1):226. doi: 10.1186/s40168-021-01107-9 [25] KOUTZOUMIS D N, VERGARA M, PINO J, et al. Alterations of the gut microbiota with antibiotics protects dopamine neuron loss and improve motor deficits in a pharmacological rodent model of Parkinson's disease[J]. Experimental Neurology,2020,325:113159. doi: 10.1016/j.expneurol.2019.113159 [26] KANG Y, KANG X, ZHANG H, et al. Gut microbiota and Parkinson's disease: Implications for faecal microbiota transplantation therapy [J]. ASN Neuro, 2021, 13: 17590914211016217. [27] YIU J H, DORWEILER B, WOO C W. Interaction between gut microbiota and toll-like receptor: From immunity to metabolism[J]. Journal of Molecular Medicine (Berlin),2017,95(1):13−20. doi: 10.1007/s00109-016-1474-4 [28] SUN M F, SHEN Y Q. Dysbiosis of gut microbiota and microbial metabolites in Parkinson's disease[J]. Ageing Research Reviews,2018,45:53−61. doi: 10.1016/j.arr.2018.04.004 [29] PIETRUCCI D, CERRONI R, UNIDA V, et al. Dysbiosis of gut microbiota in a selected population of Parkinson's patients[J]. Parkinsonism & Related Disorders,2019,65:124−130. [30] AHO V T E, PEREIRA P A B, VOUTILAINEN S, et al. Gut microbiota in Parkinson's disease: Temporal stability and relations to disease progression[J]. EBioMedicine,2019,44:691−707. doi: 10.1016/j.ebiom.2019.05.064 [31] LIN C H, CHEN C C, CHIANG H L, et al. Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson's disease[J]. Journal of Neuroinflammation,2019,16(1):129. doi: 10.1186/s12974-019-1528-y [32] CIRSTEA M S, YU A C, GOLZ E, et al. Microbiota composition and metabolism are associated with gut function in Parkinson's disease[J]. Movement Disorders,2020,35(7):1208−1217. doi: 10.1002/mds.28052 [33] VASCELLARI S, PALMAS V, MELIS M, et al. Gut microbiota and metabolome alterations associated with Parkinson's disease[J]. mSystems,2020,5(5):e00561−620. [34] BARICHELLA M, SEVERGNINI M, CILIA R, et al. Unraveling gut microbiota in Parkinson's disease and atypical parkinsonism[J]. Movement Disorders,2019,34(3):396−405. doi: 10.1002/mds.27581 [35] UNGER M M, SPIEGEL J, DILLMANN K U, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls[J]. Parkinsonism & Related Disorders,2016,32:66−72. [36] TAN A H, HOR J W, CHONG C W, et al. Probiotics for Parkinson's disease: Current evidence and future directions[J]. JGH Open,2021,5(4):414−419. doi: 10.1002/jgh3.12450 [37] MUKHERJEE A, BISWAS A, DAS S K. Gut dysfunction in Parkinson's disease[J]. World Journal of Gastroenterology,2016,22(25):5742−5752. doi: 10.3748/wjg.v22.i25.5742 [38] TSAO S P, NURRAHMA B A, KUMAR R, et al. Probiotic enhancement of antioxidant capacity and alterations of gut microbiota composition in 6-hydroxydopamin-induced Parkinson's disease rats[J]. Antioxidants (Basel),2021,10(11):1823. doi: 10.3390/antiox10111823 [39] IBRAHIM A, ALI R A R, MANAF M R A, et al. Multi-strain probiotics (Hexbio) containing MCP BCMC strains improved constipation and gut motility in Parkinson's disease: A randomised controlled trial[J]. PLoS One,2020,15(12):e0244680. doi: 10.1371/journal.pone.0244680 [40] TAN A H, LIM S Y, CHONG K K, et al. Probiotics for constipation in Parkinson disease: A randomized placebo-controlled study[J]. Neurology,2021,96(5):e772−e782. [41] BARICHELLA M, PACCHETTI C, BOLLIRI C, et al. Probiotics and prebiotic fiber for constipation associated with Parkinson disease: An RCT[J]. Neurology,2016,87(12):1274−1280. doi: 10.1212/WNL.0000000000003127 [42] GEORGESCU D, ANCUSA O E, GEORGESCU L A, et al. Nonmotor gastrointestinal disorders in older patients with Parkinson's disease: Is there hope?[J]. Clinical Interventions in Aging,2016,11:1601−1608. doi: 10.2147/CIA.S106284 [43] TAMTAJI O R, TAGHIZADEH M, DANESHVAR KAKHAKI R, et al. Clinical and metabolic response to probiotic administration in people with Parkinson's disease: A randomized, double-blind, placebo-controlled trial[J]. Clinical Nutrition,2019,38(3):1031−1035. doi: 10.1016/j.clnu.2018.05.018 [44] HSIEH T H, KUO C W, HSIEH K H, et al. Probiotics alleviate the progressive deterioration of motor functions in a mouse model of Parkinson's disease[J]. Brain Sci,2020,10(4):206. doi: 10.3390/brainsci10040206 [45] ISHII T, FURUOKA H, KAYA M, et al. Oral administration of probiotic bifidobacterium breve improves facilitation of hippocampal memory extinction via restoration of aberrant higher induction of neuropsin in an MPTP-induced mouse model of Parkinson's disease[J]. Biomedicines,2021,9(2):167. doi: 10.3390/biomedicines9020167 [46] ALIPOUR NOSRANI E, TAMTAJI O R, ALIBOLANDI Z, et al. Neuroprotective effects of probiotics bacteria on animal model of Parkinson's disease induced by 6-hydroxydopamine: A behavioral, biochemical, and histological study[J]. J Immunoassay Immunochem,2021,42(2):106−120. doi: 10.1080/15321819.2020.1833917 [47] VAN ZYL W F, DEANE S M, DICKS L M T. Molecular insights into probiotic mechanisms of action employed against intestinal pathogenic bacteria[J]. Gut Microbes,2020,12(1):1831339. doi: 10.1080/19490976.2020.1831339 [48] WANG L, ZHAO Z, ZHAO L, et al. Lactobacillus plantarum DP189 reduces α-SYN aggravation in MPTP-induced Parkinson's disease mice via regulating oxidative damage, inflammation, and gut microbiota disorder[J]. Journal of Agricultural and Food Chemistry,2022,70(4):1163−1173. doi: 10.1021/acs.jafc.1c07711 [49] MAROGIANNI C, SOKRATOUS M, DARDIOTIS E, et al. Neurodegeneration and inflammation-an interesting interplay in Parkinson's disease[J]. International Journal of Molecular Sciences,2020,21(22):8421. doi: 10.3390/ijms21228421 [50] BORZABADI S, ORYAN S, EIDI A, et al. The effects of probiotic supplementation on gene expression related to inflammation, insulin and lipid in patients with Parkinson's disease: A randomized, double-blind, placebocontrolled trial[J]. Arch Iran Med,2018,21(7):289−295. [51] PEREZ VISÑUK D, SAVOY DE GIORI G, LEBLANC J G, et al. Neuroprotective effects associated with immune modulation by selected lactic acid bacteria in a Parkinson's disease model[J]. Nutrition,2020,79-80:110995. doi: 10.1016/j.nut.2020.110995 [52] CASTELLI V, D'ANGELO M, LOMBARDI F, et al. Effects of the probiotic formulation SLAB51 in in vitro and in vivo Parkinson's disease models[J]. Aging,2020,12(5):4641−4659. doi: 10.18632/aging.102927 [53] MAGISTRELLI L, AMORUSO A, MOGNA L, et al. Probiotics may have beneficial effects in Parkinson's disease: In vitro evidence[J]. Front Immunol,2019,10:969. doi: 10.3389/fimmu.2019.00969 [54] HOU Y, LI X, LIU C, et al. Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease[J]. Experimental Gerontology,2021,150:111376. doi: 10.1016/j.exger.2021.111376 [55] GUO J D, ZHAO X, LI Y, et al. Damage to dopaminergic neurons by oxidative stress in Parkinson's disease (Review)[J]. International Journal of Molecular Medicine,2018,41(4):1817−1825. [56] NURRAHMA B A, TSAO S P, WU C H, et al. Probiotic supplementation facilitates recovery of 6-OHDA-induced motor deficit via improving mitochondrial function and energy metabolism[J]. Front Aging Neurosci,2021,13:668775. doi: 10.3389/fnagi.2021.668775 [57] NASROLAHI A, MAHMOUDI J, AKBARZADEH A, et al. Neurotrophic factors hold promise for the future of Parkinson's disease treatment: Is there a light at the end of the tunnel?[J]. Reviews in the Neurosciences,2018,29(5):475−489. doi: 10.1515/revneuro-2017-0040 [58] PALASZ E, WYSOCKA A, GASIOROWSKA A, et al. BDNF as a promising therapeutic agent in Parkinson's disease[J]. International Journal of Molecular Sciences,2020,21(3):1170. doi: 10.3390/ijms21031170 [59] WONG C E D, HUA K, MONIS S, et al. Gdnf affects early diencephalic dopaminergic neuron development through regulation of differentiation-associated transcription factors in zebrafish[J]. Journal of Neurochemistry,2021,156(4):481−498. doi: 10.1111/jnc.15108 [60] LIAO J F, CHENG Y F, YOU S T, et al. Lactobacillus plantarum PS128 alleviates neurodegenerative progression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse models of Parkinson's disease[J]. Brain Behav Immun,2020,90:26−46. doi: 10.1016/j.bbi.2020.07.036 [61] SRIVASTAV S, NEUPANE S, BHURTEL S, et al. Probiotics mixture increases butyrate, and subsequently rescues the nigral dopaminergic neurons from MPTP and rotenone-induced neurotoxicity[J]. Journal of Nutritional Biochemistry,2019,69:73−86. doi: 10.1016/j.jnutbio.2019.03.021 -
下载: 
点击查看大图
表(2)
计量
- 文章访问数: 51
- HTML全文浏览量: 61
- PDF下载量: 0
- 被引次数: 0
京公网安备 11010502036328号 京ICP备17033152号