The potential of mesenchymal stem cells in regulating the gut-brain axis in the treatment of neurological diseases

doi:10.3877/cma.j.issn.2095-1221.2024.05.007

Abstract

Abstract:

The gut-brain axis is the bidirectional regulation between the gastrointestinal tract and the central nervous system. In recent years， the gut-brain axis has become a new research hotspot，and many studies have explored the relationship between gut microbiota and nervous system diseases.Stem cell therapy is a regenerative medicine treatment method. Mesenchymal stem cells （MSCs） have shown good efficacy in improving neuropathological injury and intestinal inflammation. The current article describes the relationship between the gut-brain axis and several common nervous system diseases and the key role of the gut-brain axis in disease progression， pointing out the advantages and potential of mesenchymal stem cells in regulating gut-brain axis in the treatment of nervous system diseases， and reviews the application progress of mesenchymal stem cells in regulating the gut-brain axis in the treatment of nervous system diseases， providing new ideas for the treatment of nervous system diseases.

Key words: Mesenchymal stem cells, Stem cell therapy, Gut-brain axis, Gut microbiota, Nervous system disease

Junnan Wang, Ye Liu, Ruohan Li, Qingsong Ye. The potential of mesenchymal stem cells in regulating the gut-brain axis in the treatment of neurological diseases[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(05): 313-319.

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References 69

1	Levy M， Kolodziejczyk AA， Thaiss CA， et al. Dysbiosis and the immune system［J］. Nat Rev Immunol， 2017， 17（4）：219-232.
2	Cryan JF， O'Riordan KJ， Cowan CSM， et al. The microbiota-gut-brain axis［J］. Physiol Rev， 2019， 99（4）：1877-2013.
3	Bharti R， Grimm DG. Current challenges and best-practice protocols for microbiome analysis［J］. Brief Bioinform， 2021， 22（1）：178-193.
4	Fang P， Kazmi SA， Jameson KG， et al. The microbiome as a modifier of neurodegenerative disease risk［J］. Cell Host Microbe， 2020，28（2）：201-222.
5	Agirman G， Yu KB， Hsiao EY. Signaling inflammation across the gutbrain axis［J］. Science， 2021， 374（6571）：1087-1092.
6	Yokokawa K， Iwahara N， Hisahara S， et al. Transplantation of mesenchymal stem cells improves amyloid-β pathology by modifying microglial function and suppressing oxidative stress［J］. J Alzheimers Dis， 2019， 72（3）：867-884.
7	Wang SS， Jia J， Wang Z. Mesenchymal stem cell-derived extracellular vesicles suppresses iNOS expression and ameliorates neural impairment in Alzheimer's disease mice［J］. J Alzheimers Dis， 2018，61（3）：1005-1013.
8	王娟，刘晔，熊威，等. 间充质干细胞缓解阿尔茨海默病氧化应激的新思路［J/OL］. 中华细胞与干细胞杂志（电子版）， 2024， 14（2）：93-106.
9	Hoegenauer C， Hammer HF， Mahnert A， et al. Methanogenic archaea in the human gastrointestinal tract［J］. Nat Rev Gastroenterol Hepatol，2022， 19（12）：805-813.
10	Needham BD， Kaddurah-Daouk R， Mazmanian S K. Gut microbial molecules in behavioural and neurodegenerative conditions［J］. Nat Rev Neurosci， 2020， 21（12）：717-731.
11	Zou P， Yang F， Ding Y， et al. Lipopolysaccharide downregulates the expression of ZO-1 protein through the Akt pathway［J］. BMC Infect Dis， 2022， 22（1）：774. doi： 10.1186/s12879-022-07752-1.
12	Jiang M， Zhang X， Yan X， et al. GSK3β is involved in promoting Alzheimer's disease pathologies following chronic systemic exposure to Porphyromonas gingivalis lipopolysaccharide in amyloid precursor proteinNL-F/NL-F knock-in mice［J］. Brain Behav Immun， 2021， 98：1-12.
13	Wang Q， Yang Q， Liu X. The microbiota-gut-brain axis and neurodevelopmental disorders［J］. Protein Cell， 2023， 14（10）：762-775.
14	Mayer EA， Nance K， Chen S. The gut-brain axis［J］. Annu Rev Med，2022， 73：439-453.
15	Gong W， Guo P， Li Y， et al. Role of the gut-brain axis in the shared genetic etiology between gastrointestinal tract diseases and psychiatric disorders： a genome-wide pleiotropic analysis［J］. JAMA psychiatry，2023， 80（4）：360-370.
16	Loh J S， Mak W Q， Tan LKS， et al. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases［J］. Signal Transduct Target Ther， 2024， 9（1）：37.doi： 10.1038/s41392-024-01743-1.
17	Morais LH， Schreiber HL， Mazmanian SK. The gut microbiota-brain axis in behaviour and brain disorders［J］. Nat Rev Microbiol， 2021，19（4）：241-255.
18	Yamashiro K， Tanaka R， Urabe T， et al. Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke［J］. PloS One， 2017， 12（2）：e0171521. doi： 10.1371/journal.pone.0171521.
19	Honarpisheh P， Bryan RM， McCullough LD. Aging microbiota-gutbrain axis in stroke risk and outcome［J］. Circ Res， 2022， 130（8）：1112-1144.
20	Parr E， Ferdinand P， Roffe C. Management of acute stroke in the older person［J］. Geriatrics （Basel）， 2017， 2（3）：27. doi： 10.3390/geriatrics 2030027.
21	Chidambaram SB， Rathipriya AG， Mahalakshmi AM， et al. The influence of gut dysbiosis in the pathogenesis and management of ischemic stroke［J］. Cells， 2022， 11（7）：1239. doi：10.3390/cells1107 1239.
22	Tan C， Wu Q， Wang H， et al. Dysbiosis of gut microbiota and shortchain fatty acids in acute ischemic stroke and the subsequent risk for poor functional outcomes［J］. JPEN J Parenter Enteral Nutr， 2021，45（3）：518-529.
23	Yu X， Zhou G， Shao B， et al. Gut microbiota dysbiosis induced by intracerebral hemorrhage aggravates neuroinflammation in mice［J］.Front Microbiol， 2021， 12：647304. doi： 10.3389/fmicb.2021.647304.
24	Chen R， Xu Y， Wu P， et al. Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota［J］. Pharmacol Res， 2019， 148：104403.doi： 10.1016/j.phrs.2019.104403.
25	Li S， Zhao X， Lin F， et al. Gut flora mediates the rapid tolerance of electroacupuncture on ischemic stroke by activating melatonin receptor through regulating indole-3-propionic acid［J］. Am J Chin Med， 2022，50（4）：979-1006.
26	Xu K， Gao X， Xia G， et al. Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn［J］. Gut， 2021， 8：gutjnl-2020-323263. doi： 10.1136/gutjnl-2020-323263.
27	de Oliveira Araújo R， Villoria GEM， Luiz RR， et al. Association between periodontitis and Alzheimer's disease and its impact on the self-perceived oral health status： a case-control study［J］. Clin Oral Investig， 2021， 25（2）：555-562.
28	Seo DO， Holtzman DM. Current understanding of the Alzheimer's disease-associated microbiome and therapeutic strategies［J］. Exp Mol Med， 2024， 56（1）：86-94.
29	Friedland RP， Chapman MR. The role of microbial amyloid in neurodegeneration［J］. PLoS Pathog， 2017， 13（12）：e1006654. doi：10.1371/journal.ppat.1006654.
30	Vogt NM， Kerby RL， Dill-McFarland KA， et al. Gut microbiome alterations in Alzheimer's disease［J］. Sci Rep， 2017， 7（1）：13537. doi：10.1038/s41598-017-13601-y.
31	Cattaneo A， Cattane N， Galluzzi S， et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly［J］. Neurobiol Aging， 2017， 49：60-68.
32	Brandscheid C， Schuck F， Reinhardt S， et al. Altered gut microbiome composition and tryptic activity of the 5xFAD Alzheimer's mouse model［J］. J Alzheimers Dis， 2017， 56（2）：775-788.
33	Kim MS， Kim Y， Choi H， et al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model［J］. Gut， 2020， 69（2）：283-294.
34	Wang ZH， Gong K， Liu X， et al. C/EBPβ regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer's disease［J］. Nat Commun， 2018， 9（1）：1784. doi： 10.1038/s41467-018-04120-z.
35	Chen C， Zhou Y， Wang H， et al. Gut inflammation triggers C/EBPβ/δ-secretase-dependent gut-to-brain propagation of Aβ and Tau fibrils in Alzheimer's disease［J］. EMBO J， 2021， 40（17）：e106320. doi： 10.15252/embj.2020106320.
36	Chen C， Liao J， Xia Y， et al. Gut microbiota regulate Alzheimer's disease pathologies and cognitive disorders via PUFA-associated neuroinflammation［J］. Gut， 2022， 71（11）：2233-2252.
37	Xia Y， Xiao Y， Wang ZH， et al. Bacteroides Fragilis in the gut microbiomes of Alzheimer's disease activates microglia and triggers pathogenesis in neuronal C/EBPβ transgenic mice［J］. Nat Commun，2023， 14（1）：5471. doi： 10.1038/s41467-023-41283-w.
38	Claudino Dos Santos JC， Lima MPP， Brito GAC， et al. Role of enteric glia and microbiota-gut-brain axis in parkinson disease pathogenesis［J］.Ageing Res Rev， 2023， 84：101812. doi： 10.1016/j.arr.2022.101812.
39	Ye H， Robak LA， Yu M， et al. Genetics and Pathogenesis of Parkinson's Syndrome［J］. Annu Rev Pathol， 2023， 18：95-121.
40	Chahine LM， Beach TG， Brumm MC， et al. In vivo distribution of α-synuclein in multiple tissues and biofluids in Parkinson disease［J］.Neurology， 2020， 95（9）：e1267-e1284.
41	Stokholm MG， Danielsen EH， Hamilton-Dutoit SJ， et al. Pathological α-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients［J］. Ann Neurol， 2016， 79（6）：940-949.
42	Tan AH， Lim SY， Lang AE. The microbiome-gut-brain axis in Parkinson disease-from basic research to the clinic［J］. Nat Rev Neurol，2022， 18（8）：476-495.
43	Kim S， Kwon SH， Kam TI， 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.e7.
44	Bassil F， Brown HJ， Pattabhiraman S， et al. Amyloid-Beta （Aβ） plaques promote seeding and spreading of alpha-synuclein and Tau in a mouse model of lewy body disorders with Aβ pathology［J］. Neuron， 2020，105（2）：260-275.e6.
45	Li N， Hua J. Interactions between mesenchymal stem cells and the immune system［J］. Cell Mol Life Sci， 2017， 74（13）：2345-2360.
46	Andrzejewska A， Dabrowska S， Lukomska B， et al. Mesenchymal stem cells for neurological disorders［J］. Adv Sci （Weinh）， 2021，8（7）：2002944.doi： 10.1002/advs.202002944.
47	冯佳，谢芳莘，杨嘉洁，等. TIMP2 基因修饰间充质干细胞治疗阿尔兹海默症的实验小鼠模型研究［J］. 中国输血杂志， 2020，33（5）：441-445.
48	卜美玲，穆晓颖，赵晨阳. 脂肪间充质干细胞脑内定向移植治疗大鼠脑出血的机制研究［J］. 中国当代医药， 2024， 31（20）：14-17.
49	Li Y， Huang J， Wang J， et al. Human umbilical cord-derived mesenchymal stem cell transplantation supplemented with curcumin improves the outcomes of ischemic stroke via AKT/GSK-3β/β-TrCP/Nrf2 axis［J］. J Neuroinflammation， 2023， 20（1）：49.doi： 10.1186/s12974-023-02738-5.
50	叶青松，彭友俭，骆瑜. 细胞外泌体的分离提取标准化及临床转化进展［J］. 口腔疾病防治， 2022， 30（9）：609-619.
51	刘君鹏，李云飞，李永坤. 间充质干细胞外泌体对缺血性脑卒中大鼠神经功能恢复的影响［J］. 中国当代医药， 2024， 31（17）：4-8.
52	孙逸梅，毛诗慧，李琳，等. 骨髓间充质干细胞源性外泌体促进小胶质细胞/巨噬细胞M2 极化抑制急性期脑缺血大鼠炎症反应［J］.中国药科大学学报， 2023， 54（5）：599-606.
53	Harrell CR， Jovicic N， Djonov V， et al. Mesenchymal stem cellderived exosomes and other extracellular vesicles as new remedies in the therapy of inflammatory diseases［J］. Cells， 2019， 8（12）：1605. doi：10.3390/cells8121605.
54	Palanisamy CP， Pei J， Alugoju P， et al. New strategies of neurodegenerative disease treatment with extracellular vesicles （EVs）derived from mesenchymal stem cells （MSCs）［J］. Theranostics， 2023，13（12）：4138-4165.
55	Zhang Q， Deng P， Chen S， et al. Electroacupuncture and human iPSC-derived small extracellular vesicles regulate the gut microbiota in ischemic stroke via the brain-gut axis［J］. Front Immunol， 2023，14：1107559.doi： 10.3389/fimmu.2023.1107559.
56	Sun J， Xu G. Mesenchymal stem cell-derived exosomal miR-150- 3p affects intracerebral hemorrhage by regulating TRAF6/NF-κB axis， gut microbiota and metabolism［J］. Stem Cell Rev Rep， 2023， 19（6）：1907-1921.
57	Zhang L， Jiang Z， Hu S， et al. GSK3β substrate-competitive inhibitors regulate the gut homeostasis and barrier function to inhibit neuroinflammation in scopolamine-induced Alzheimer's disease model mice［J］. Inflammation， 2024. doi：10.1007/s10753-024-02133-z.
58	Xiong W， Liu Y， Zhou H， et al. Human dental pulp stem cells mitigate the neuropathology and cognitive decline via AKT-GSK3β-Nrf2 pathways in Alzheimer's disease［J］. Int J Oral Sci， 2024， 16（1）：40.doi：10.1038/s41368-024-00300-4.
59	Anderson S， Prateeksha P， Das H. Dental pulp-derived stem cells reduce inflammation， accelerate wound healing and mediate M2 polarization of myeloid cells［J］. Biomedicines， 2022， 10（8）：1999. doi：10.3390/biomedicines10081999.
60	Sha S， Shen X， Cao Y， et al. Mesenchymal stem cells-derived extracellular vesicles ameliorate Alzheimer's disease in rat models via the microRNA-29c-3p/BACE1 axis and the Wnt/β-catenin pathway［J］.Aging， 2021， 13（11）：15285-15306.
61	Naaldijk Y， Jäger C， Fabian C， et al. Effect of systemic transplantation of bone marrow-derived mesenchymal stem cells on neuropathology markers in APP/PS1 Alzheimer mice［J］. Neuropathol Appl Neurobiol，2017， 43（4）：299-314.
62	Santamaria G， Brandi E， Vitola PL， et al. Intranasal delivery of mesenchymal stem cell secretome repairs the brain of Alzheimer's mice［J］. Cell Death Differ， 2021， 28（1）：203-218.
63	Losurdo M， Pedrazzoli M， D'Agostino C， et al. Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer's disease［J］. Stem Cells Transl Med， 2020， 9（9）：1068-1084.
64	Liu A， Liang X， Wang W， et al. Human umbilical cord mesenchymal stem cells ameliorate colon inflammation via modulation of gut microbiota-SCFAs-immune axis［J］. Stem Cell Res Ther， 2023，14（1）：271. doi： 10.1186/s13287-023-03471-9.
65	Lee JY， Tuazon JP， Ehrhart J， et al. Gutting the brain of inflammation：A key role of gut microbiome in human umbilical cord blood plasma therapy in Parkinson's disease model［J］. J Cell Mol Med， 2019，23（8）：5466-5474.
66	Lee JY， Tuazon JP， Corey S， et al. A gutsy move for cell-based regenerative medicine in Parkinson's disease： targeting the gut microbiome to sequester inflammation and neurotoxicity［J］. Stem Cell Rev Rep， 2019， 15（5）：690-702.
67	Lee JY， Wang ZJ， Moscatello A， et al. Inflammatory gut as a pathologic and therapeutic target in Parkinson's disease［J］. Cell Death Discov，2022， 8（1）：396.doi： 10.1038/s41420-022-01175-2.
68	Lee JY， Castelli V， Sanberg PR， et al. Probing gut participation in Parkinson's disease pathology and treatment via stem cell therapy［J］.Int J Mol Sci， 2023， 24（13）：10600.doi： 10.3390/ijms241310600.
69	Pu Y， Wu Q， Zhang Q， et al. Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice： a role of the gut-microbiota-brain axis［J］. Psychopharmacology， 2023，240（5）：1103-1118.

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