Role of short-chain fatty acids in the pathogenesis of Parkinson’s disease

Abstract

Parkinson’s disease is tightly related to enteric nervous system dysfunction and gut microbiota dysbiosis. Short-chain fatty acids are the main metabolites produced by the gut bacteria fermentation of dietary fiber and are suggested to play a key role in gut–brain cross-talk. The article presents a review of the literature on the contribution of short-chain fatty acids to the pathogenesis of Parkinson’s disease. Patients with Parkinson’s disease have higher plasma concentrations of acetate, propionate, and butyrate than controls. These changes correlate with the severity of the clinical picture of Parkinson’s disease, levels of pro-inflammatory gut bacteria and pro-inflammatory cytokines. The cause of these changes may be an over-population of the gut of Parkinson’s disease patients with bacteria such as clostridia and ruminococci, leading to regulatory immune reactions, intestinal inflammation, increased permeability of the intestinal barrier, excessive intake primarily of propionate in the central nervous system, and activation of neuroinflammation. The importance of further study of the relationship between changes in gut metabiotic, its metabolome, and the immune system T-cell in patients with Parkinson’s disease is demonstrated. Justified the study of blood plasma from patients with Parkinson’s disease using gas chromatography–mass spectrometry for the accurate, clinically relevant, assessment of the gut–brain crosstalk.

Keywords

gas chromatography–mass spectrometry / gut microbiota / metabolome / neuroinflammation / Parkinson’s disease / pathogenesis / short-chain fatty acids

References

[1] Rietdijk CD, Perez-Pardo P, Garssen J, et al. Exploring Braak’s Hypothesis of Parkinson’s Disease. Front Neurol. 2017;8:37. DOI: 10.3389/fneur.2017.00037

[2] Rietdijk C.D., Perez-Pardo P., Garssen J., et al. Exploring Braak’s Hypothesis of Parkinson’s Disease // Front. Neurol. 2017. Vol. 8. P. 37. DOI: 10.3389/fneur.2017.00037

[3] Sampson TR, Debelius JW, Thron T, et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease. Cell. 2016;167(6):1469–1480.e12. DOI: 10.1016/j.cell.2016.11.018

[4] Sampson T.R., Debelius J.W., Thron T., et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease // Cell. 2016. Vol. 167, No. 6. P. 1469–1480.e12. DOI: 10.1016/j.cell.2016.11.018

[5] Unger MM, Spiegel J, Dillmann KU, 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. DOI: 10.1016/j.parkreldis.2016.08.019

[6] 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 // Parkinsonism Relat. Disord. 2016. Vol. 32. P. 66–72. DOI: 10.1016/j.parkreldis.2016.08.019

[7] Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823–1836. DOI: 10.1042/BCJ20160510

[8] Thursby E., Juge N. Introduction to the human gut microbiota // Biochem. J. 2017. Vol. 474, No. 11. P. 1823–1836. DOI: 10.1042/BCJ20160510

[9] Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol. 2017;19(1):29–41. DOI: 10.1111/1462-2920

[10] Louis P., Flint H.J. Formation of propionate and butyrate by the human colonic microbiota // Environ. Microbiol. 2017. Vol. 19, No. 1. P. 29–41. DOI: 10.1111/1462-2920

[11] Dalile B, Van Oudenhove L, Vervliet B, Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol. 2019;16(8):461–478. DOI: 10.1038/s41575-019-0157-3

[12] Dalile B., Van Oudenhove L., Vervliet B., Verbeke K. The role of short-chain fatty acids in microbiota-gut-brain communication // Nat. Rev. Gastroenterol Hepatol. 2019. Vol. 16, No. 8. P. 461–478. DOI: 10.1038/s41575-019-0157-3

[13] Shin C, Lim Y, Lim H, Ahn TB. Plasma Short-Chain Fatty Acids in Patients with Parkinson’s Disease. Mov Disord. 2020;35(6): 1021–1027. DOI: 10.1002/mds.28016

[14] Shin C., Lim Y., Lim H., Ahn T.B. Plasma Short-Chain Fatty Acids in Patients with Parkinson’s Disease // Mov. Disord. 2020. Vol. 35, No. 6. P. 1021–1027. DOI: 10.1002/mds.28016

[15] He X, Qian Y, Xu S, et al. Plasma Short-Chain Fatty Acids Differences in Multiple System Atrophy from Parkinson’s Disease. J Parkinsons Dis. 2021;11(3):1167–1176. DOI: 10.3233/JPD-212604

[16] He X., Qian Y., Xu S., et al. Plasma Short-Chain Fatty Acids Differences in Multiple System Atrophy from Parkinson’s Disease // J. Parkinsons Dis. 2021. Vol. 11, No. 3. P. 1167–1176. DOI: 10.3233/JPD-212604

[17] Krasakov IV, Litvinenko IV, Rodionov GG, et al. Evaluation of gut microbiota in Parkinson’s disease using gas chromatography with mass spectrometric detection. Annals of clinical and experimental neurology. 2018;12(4):23–29. (In Russ.) DOI: 10.25692/ACEN.2018.4.3

[18] Красаков И.В., Литвиненко И.В., Родионов Г.Г., и др. Оценка микробиоты кишечника у пациентов с болезнью Паркинсона с помощью метода газовой хромато-масс-спектрометрии // Анналы клинической и экспериментальной неврологии. 2018. T. 12, № 4. C. 23–29. DOI: 10.25692/ACEN.2018.4.3

[19] Chen SJ, Chen CC, Liao HY, et al. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids with Gut Microbiota and Clinical Severity in Patients with Parkinson Disease. Neurology. 2022;98(8): e848–e858. DOI: 10.1212/WNL.0000000000013225

[20] Chen S.J., Chen C.C, Liao H.Y., et al. Association of Fecal and Plasma Levels of Short-Chain Fatty Acids with Gut Microbiota and Clinical Severity in Patients with Parkinson Disease // Neurology. 2022. Vol. 98, No. 8. P. e848–e858. DOI: 10.1212/WNL.0000000000013225

[21] Kelly LP, Carvey PM, Keshavarzian A, et al. Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson’s disease. Mov Disord. 2014;29(8): 999–1009. DOI: 10.1002/mds.25736

[22] Kelly L.P., Carvey P.M., Keshavarzian A., et al. Progression of intestinal permeability changes and alpha-synuclein expression in a mouse model of Parkinson’s disease // Mov. Disord. 2014. Vol. 29, No. 8. P. 999–1009. DOI: 10.1002/mds.25736

[23] Kim CH, Park J, Kim M. Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation. Immune Netw. 2014;14(6):277–288. DOI: 10.4110/in.2014.14.6.277

[24] Kim C.H., Park J., Kim M. Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation // Immune Netw. 2014. Vol. 14, No. 6. P. 277–288. DOI: 10.4110/in.2014.14.6.277

[25] Lindenberg F, Krych L, Fielden J, et al. Expression of immune regulatory genes correlate with the abundance of specific Clostridiales and Verrucomicrobia species in the equine ileum and cecum. Sci Rep. 2019;9(1):12674. DOI: 10.1038/s41598-019-49081-5

[26] Lindenberg F., Krych L., Fielden J., et al. Expression of immune regulatory genes correlate with the abundance of specific Clostridiales and Verrucomicrobia species in the equine ileum and cecum // Sci. Rep. 2019. Vol. 9, No. 1. Art. 12674. DOI: 10.1038/s41598-019-49081-5

[27] Krasakov IV, Davydova NI, Kalashnikova AA, et al. Features of innate and adaptive immunity in patients with Parkinson’s disease. Annals of clinical and experimental neurology. 2022;16(1):14–23. (In Russ.) DOI: 10.54101/ACEN.2022.1.2

[28] Красаков И.В., Давыдова Н.И., Калашникова А.А., и др. Особенности показателей врожденного и адаптивного иммунитета у пациентов с болезнью Паркинсона // Анналы клинической и экспериментальной неврологии. 2022. T. 16, № 1. C. 14–23. DOI: 10.54101/ACEN.2022.1.2

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