ISSN 2412-4036 (print)
ISSN 2713-1823 (online)

Parkinson’s disease: New methods of stimulation of deep brain structures and the role of the intestinal microbiome in pathogenesis (literature review)

L.A. Lyubskaya, N. Thanh Lam

Tver State Medical University, Tver, Russian Federation
Abstract. The article presents a literature review of current data on Parkinson’s disease, focusing on two promising areas of research: methods for stimulating deep brain structures and the influence of the gut microbiota on the development of the disease. The main types of neuromodulatory interventions (including deep brain stimulation), their mechanisms of action, clinical efficacy, and limitations of use are discussed. A separate analysis of current understanding of the role of the gut microbiome in Parkinson’s disease pathogenesis, including possible pathways of gut-brain interaction (via vagal nerve, immune system, microbial metabolites, etc.), as well as data from preclinical and clinical studies in this area is provided. The results of key publications from recent years are systematized; promising areas for further research, and potential opportunities for developing new therapeutic strategies combining neuromodulation and microbiota modification are identified in the article.

Keywords

Parkinson’s disease
deep brain stimulation
adaptive neurostimulation (aDBS)
gut-brain axis
gut microbiota
neurodegeneration
neuroinflammation
personalized medicine

References

1. Веругина Н.И., Левин О.С., Ляшенко Е.А. Роль кишечной микробиоты при болезни Паркинсона. Журнал неврологии и психиатрии им. С.С. Корсакова. 2021;121 (10–2):86–91. (Verugina NI, Levin OS, Lyashenko EA. The role of the gut microbiota in Parkinson’s disease. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2021;121(10–2):86–91 (In Russ.)).

EDN: YNSOFS. https://doi.org/10.17116/jnevro202112110286

2. Гапонов Д.О., Пригодина Е.В., Грудина Т.В., Доросевич А.Е. Современный взгляд на патогенетические механизмы прогрессирования болезни Паркинсона. РМЖ. 2018;26(12–1):66–72. (Gaponov DO, Prigodina EV, Grudina TV, Dorosevich AE. Modern view on the pathogenetic mechanisms of Parkinson’s disease progression. Russkiy meditsinskiy zhurnal = Russian Medical Journal. 2018;26(12–1):66–72 (In Russ.)). EDN: YOCITJ.

3. Султанова С.Г., Федорова Н.В., Веругина Н.И., Смоленцева И.Г. Влияние двусторонней глубокой стимуляции субталамического ядра на ходьбу и равновесие у пациентов с болезнью Паркинсона. Журнал неврологии и психиатрии им. С.С. Корсакова. 2025:125(3):94–101. (Sultanova SG, Fedorova NV, Verugina NI, Smolentseva IG. The effect of bilateral subthalamic nucleus deep brain stimulation on gait and balance in patients with Parkinson’s disease. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry. 2025;125(3):94–101 (In Russ.)).

EDN: FTKFRH. https://doi.org/10.17116/jnevro202512503194

4. Тютина Р.Р., Пилипович А.А., Голубев В.Л., Данилов Ал.Б. Микробиота и болезнь Паркинсона (обзор). Медицинский алфавит. 2020;(1):10–14. (Tyutina RR, Pilipovich AA, Golubev VL, Danilov AlB. Microbiota and Parkinson’s disease (overview). Meditsinskiy alfavit = Medical Alphabet. 2020;(1):10–14 (In Russ.)).

EDN: CQKDPE. https://doi.org/10.33667/2078-5631-2020-1-10-14

5. Левин О.С., Артемьев Д.В., Бриль Е.В., Кулуа Т.К. Болезнь Паркинсона: современные подходы к диагностике и лечению. Практическая медицина. 2017;1(1):45–51. (Levin OS, Artemyev DV, Bril EV, Kulua TK. Parkinson's disease: Modern approaches to diagnosis and treatment. Prakticheskaya meditsina = Practical medicine. 2017;1(1):45–51 (In Russ.)). EDN: YHZKNP.

6. Бриль Е.В., Томский А.А., Гамалея А.А., Поддубская А.А., Кесарев Д.Г., Федорова Н.В. Синдром отмены нейростимуляции у пациентов с болезнью Паркинсона – редкое неотложное состояние в неврологии и нейрохирургии. Анналы клинической и экспериментальной неврологии. 2024;18(3):91–102. (Bril EV, Tomskiy AA, Gamaleya AA, Poddubskaya AA, Kesarev DG, Fedorova NV. Deep brain stimulation withdrawal syndrome, a rare life-threatening condition in neurology and neurosurgery. Annaly klinicheskoy i eksperimental’noy nevrologii = Annals of Clinical and Experimental Neurology. 2024;18(3):91–102 (In Russ.)). EDN: IAQKXW.

https://doi.org/10.17816/ACEN.1095

7. Benabid AL, Chabardes S, Mitrofanis J, Pollak P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol. 2009;8(1):67–81.

PMID: 19081516. https://doi.org/10.1016/S1474-4422(08)70291-6

8. Lozano AM, Lipsman N, Bergman H, Brown P, Chabardes S, Chang JW et al. Deep brain stimulation: Current challenges and future directions. Nat Rev Neurol. 2019;15(3):148–60.

PMID: 30683913. PMCID: PMC6397644. https://doi.org/10.1038/s41582-018-0128-2

9. Krauss JK, Lipsman N, Aziz T, Boutet A, Brown P, Chang JW et al. Technology of deep brain stimulation: Current status and future trends. Nat Rev Neurol. 2021;17(2):75–87.

PMID: 33244188. PMCID: PMC7116699. https://doi.org/10.1038/s41582-020-00426-z

10. Little S, Brown P. The functional role of beta oscillations in Parkinson’s disease. Parkinsonism Relat Disord. 2014;20 Suppl 1:S44–48.

PMID: 24262186. https://doi.org/10.1016/S1353-8020(13)70013-0

11. Bronte-Stewart HM, Beudel M, Ostrem JL, Little S, Almeida L, Ramirez-Zamora A et al.; ADAPT-PD Investigators. Long-term personalized adaptive deep brain stimulation in Parkinson disease: a nonrandomized clinical trial. JAMA Neurol. 2025;82(11):1171–80.

PMID: 40982287. PMCID: PMC12455485. https://doi.org/10.1001/jamaneurol.2025.2781

12. Guidetti M, Marceglia S, Bocci T, Duncan R, Fasano A, Foote KD et al. Physical therapy in patients with Parkinson’s disease treated with deep brain stimulation: A Delphi panel study. medRxiv (Preprint). 2024:2024.09.20.24314037.

PMID: 39399050. PMCID: PMC11469472. https://doi.org/10.1101/2024.09.20.24314037. Update in: J Neuroeng Rehabil. 2025;22(1):80. https://doi.org/10.1186/s12984-025-01616-w

13. Oulu University Repository. Kahkola J. Personalized deep brain stimulation for Parkinson’s disease. 2024.

URL: https://www.oulu.fi/en/theses/personalized-deep-brain-stimulation-for-parkinsons-disease (date of access – 10.06.2026).

14. Troster AI. Developments in the prediction of cognitive changes following deep brain stimulation in persons with Parkinson’s disease. Expert Rev Neurother. 2024;24(7):643–59.

PMID: 38814926. https://doi.org/10.1080/14737175.2024.236012

15. Neumann WJ, Gilron R, Little S, Tinkhauser G. Adaptive deep brain stimulation: From experimental evidence toward practical implementation. Mov Disord. 2023;38(6):937–48.

PMID: 37148553. https://doi.org/10.1002/mds.29415

16. Lozano AM, Lipsman N, Bergman H, Brown P, Chabardes S, Chang JW et al. Deep brain stimulation: Current challenges and future directions. Nat Rev Neurol. 2019;15(3):148–60.

PMID: 30683913. PMCID: PMC6397644. https://doi.org/10.1038/s41582-018-0128-2

17. Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K et al.; German Parkinson Study Group, Neurostimulation Section. A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2006;355(9):896–908.

PMID: 16943402. https://doi.org/10.1056/NEJMoa060281. Erratum in: N Engl J Med. 2006;355(12):1289.

18. Limousin P, Foltynie T. Long-term outcomes of deep brain stimulation in Parkinson disease. Nat Rev Neurol. 2019;15(4):234–42.

PMID: 30778210. https://doi.org/10.1038/s41582-019-0145-9

19. Бриль Е.В., Томский А.А., Гамалея А.А. Место DBS в лечении болезни Паркинсона. Бюллетень Национального общества по изучению болезни Паркинсона и расстройств движений. 2022;(2):23–25. (Bril EV, Tomsky AA, Gamaleya AA. The role of DBS in the treatment of Parkinson’s disease. Byulleten’ Natsional’nogo obshchestva po izucheniyu bolezni Parkinsona i rasstroystv dvizheniy = Bulletin of the National Society for the Study of Parkinson’s Disease and Movement Disorders. 2022;(2):23–25 (In Russ.)).

EDN: PHSNCY. https://doi.org/10.24412/2226-079X-2022-12428

20. Sandoval-Pistorius SS, Hacker ML, Waters AC, Wang J, Provenza NR, de Hemptinne C et al. Advances in deep brain stimulation: From mechanisms to applications. J Neurosci. 2023;43(45):7575-7586.

PMID: 37940596. PMCID: PMC10634582. https://doi.org/10.1523/JNEUROSCI.1427-23.2023.

21. Fenoy AJ, Simpson RK Jr. Risks of common complications in deep brain stimulation surgery: Management and avoidance. J Neurosurg. 2014;120(1):132–39.

PMID: 24236657. https://doi.org/10.3171/2013.10.JNS131225

22. Conway ZJ, Silburn PA, Perera T, O’Maley K, Cole MH. Low-frequency STN-DBS provides acute gait improvements in Parkinson’s disease: A double-blinded randomised cross-over feasibility trial. J Neuroeng Rehabil. 2021;18(1):125.

PMID: 34376190. PMCID: PMC8353795. https://doi.org/10.1186/s12984-021-00921-4

23. Hong J, Xie H, Chen Y, Liu D, Wang T, Xiong K, Mao Z. Effects of STN-DBS on cognition and mood in young-onset Parkinson’s disease: A two-year follow-up. Front Aging Neurosci. 2024;15:1177889.

PMID: 38292047. PMCID: PMC10824910. https://doi.org/10.3389/fnagi.2023.1177889

24. Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M et al. The microbiota-gut-brain axis. Physiol Rev. 2019;99(4):1877–2013.

PMID: 31460832. https://doi.org/10.1152/physrev.00018.2018

25. Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018;1693(Pt B):128–33.

PMID: 29903615. PMCID: PMC6005194. https://doi.org/10.1016/j.brainres.2018.03.015

26. Tan AH, Lim SY, Lang AE. The microbiome-gut-brain axis in Parkinson disease – from basic research to the clinic. Nat Rev Neurol. 2022;18(8):476–95. PMID: 35750883. https://doi.org/10.1038/s41582-022-00681-2

27. Li X, Hao X, Chen C, Zhai C, Pan T, Zhou X et al. Trends and hotspots on the relationship between gut microbiota and Parkinson’s disease: A bibliometric analysis. Front Cell Infect Microbiol. 2024;14:1421270.

PMID: 39403202. PMCID: PMC11472709. https://doi.org/10.3389/fcimb.2024.1421270

28. Jin X, Wei J, Min X, Fan Y, Yuan Z, Du Z et al. Gut microbiota and Parkinson’s disease: Exploring pathogenesis and potential therapeutic strategies. iScience. 2025;28(2):109012.

PMID: 41585498. PMCID: PMC12830195. https://doi.org/10.1016/j.isci.2025.114185

29. Beas R, Riva‑Moscoso A, Montalvan‑Sanchez E, Príncipe‑Meneses FS, Aljaras R, Ramirez‑Rojas M et al. Prevalence of small intestinal bacterial overgrowth in patients with gastroparesis: A systematic review and meta‑analysis. Gastroenterol Hepatol Bed Bench. 2023;16(1):438–47.

PMID: 37070116. PMCID: PMC10105503. https://doi.org/10.22037/ghfbb.v16i1.2652

30. Braak H, Rüb U, Gai WP, Del Tredici K. Idiopathic Parkinson’s disease: Possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna). 2003;110(5):517–36.

PMID: 12721813. https://doi.org/10.1007/s00702-002-0808-2

31. Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S et al. Transneuronal Propagation of pathologic α-synuclein from the gut to the brain models Parkinson’s disease. Neuron. 2019;103(4):627–41.e7.

PMID: 31255487. PMCID: PMC6706297. https://doi.org/10.1016/j.neuron.2019.05.035

32. Svensson E, Horvath-Puho E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P, Sørensen HT. Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol. 2015;78(4):522–529.

PMID: 26031848. https://doi.org/10.1002/ana.24448

33. Jia X, Wang Q, Liu M, Ding J. The interplay between gut microbiota and the brain-gut axis in Parkinson’s disease treatment. Front Neurol. 2024;15:1415463.

PMID: 38867886. PMCID: PMC11168434. https://doi.org/10.3389/fneur.2024.1415463

34. Houser MC, Tansey MG. The gut-brain axis: Is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis. 2017;3:3.

PMID: 28649603. PMCID: PMC5445611. https://doi.org/10.1038/s41531-016-0002-0

35. Perez-Pardo P, Dodiya HB, Engen PA, Forsyth CB, Huschens AM, Shaikh M et al. Role of TLR4 in the gut-brain axis in Parkinson’s disease: A translational study from mice to human. Gut. 2019;68(5):829–43.

PMID: 30554160. https://doi.org/10.1136/gutjnl-2018-316844

36. ORBilu. University of Luxemburg. Open Repository and Bibliography. Novikova P. Systematic characterization of human gut microbiome in relation to Parkinson’s disease. URL: https://orbilu.uni.lu/handle/10993/62565 (date of access – 10.06.2026).

37. Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Burmann J et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord. 2016;32:66–72.

PMID: 27591074. https://doi.org/10.1016/j.parkreldis.2016.08.019

38. Wang L, Cui Y, Han B, Du Y, Salewala KS, Wang S et al. Gut microbiota and Parkinson’s disease. Chin Med J (Engl). 2025;138(3):289–97.

PMID: 39501822. PMCID: PMC11771718. https://doi.org/10.1097/CM9.0000000000003318

39. Chao YX, Gulam MY, Chia NSJ, Feng L, Rotzschke O, Tan EK. Gut-brain axis: Potential factors involved in the pathogenesis of Parkinson’s disease. Front Neurol. 2020;11:849.

PMID: 32982910. PMCID: PMC7477379. https://doi.org/10.3389/fneur.2020.00849. Erratum in: Front Neurol. 2020;11:625446.

https://doi.org/10.3389/fneur.2020.625446.

About the Authors

Lyubov A. Lyubskaya, MD, PhD (Medicine), associate professor of the Department of outpatient therapy, Tver State Medical University, Tver, Russian Federation.
E-mail: lyubskayala@tvgmu.ru
ORCID: https://orcid.org/0009-0009-3915-3657. eLibrary SPIN: 9854-6343. Scopus ID: 6701571167
Nguyen Thanh Lam, sixth-year student of the Faculty of general medicine, Tver State Medical University, Tver, Russian Federation, Vietnam.
E-mail: thanhlam9a2512000@gmail.com
ORCID: https://orcid.org/0009-0005-6048-8129. eLibrary SPIN: 6586-5347

Similar Articles