Preview

Bulletin of Siberian Medicine

Advanced search

Diagnostic potential of gut microbiota in Parkinson’s disease

https://doi.org/10.20538/1682-0363-2019-4-92-101

Abstract

Background. Nowadays many efforts are taken in searching for Parkinson’s disease biomarkers, especially for an early recognition of the disease. The gut microbiota is one of the potential sources of biomarkers, changes in the composition of which in PD are actively studied.

The aim of this study is to identify microbiota biomarkers in the Parkinson’s disease with an estimated accuracy of the diagnostics, including differential diagnostics, relative to other neurological diseases for patients of the Russian population.

Material and methods. One hundred ninety-two metagenomics profiles from patients with Parkinson’s disease (n = 93), people with other neurological diagnoses (n = 33), and healthy controls (n = 66) were included in this study. These profiles were obtained with amplicon sequencing of bacterial 16S rRNA genes. Classifying models were made using the naive Bayes classifier, the artificial neural network, support vector machine, generalized linear model, and partial least squares regression.

As a result we established that an optimal classification by the composition of the gut microbiota on the validation sample (sensitivity 91.30%, specificity 91.67% at 91.49% accuracy) amid patients was demonstrated with a naive Bayes classifier using the representation of the following genera as predictors: Christensenella, Methanobrevibacter, Leuconostoc, Enterococcus, Catabacter, Desulfovibrio, Sphingomonas, Yokenella, Atopobium, Fusicatenibacter, Cloacibacillus, Bulleidia, Acetanaerobacterium, and Staphylococcus.

Conclusions. Information of the gut microbiota taxonomic composition may be used in differential diagnosis of Parkinson’s disease. 

About the Authors

V. A. Petrov
Siberian State Medical University (SSMU)
Russian Federation

Junior Researcher, Central Research Laboratory,

2, Moscow Trakt, Tomsk, 634050



V. M. Alifirova
Siberian State Medical University (SSMU)
Russian Federation

DM, Professor, Head of the Neurology and Neurosurgery Department,

2, Moscow Trakt, Tomsk, 634050



I. V. Saltykova
Siberian State Medical University (SSMU)
Russian Federation

PhD, Researcher, Central Research Laboratory,

2, Moscow Trakt, Tomsk, 634050



I. A. Zhukova
Siberian State Medical University (SSMU)
Russian Federation

PhD, Associate Professor, Neurology and Neurosurgery Department,

2, Moscow Trakt, Tomsk, 634050



N. G. Zhukova
Siberian State Medical University (SSMU)
Russian Federation

DM, Professor, Neurology and Neurosurgery Department,

2, Moscow Trakt, Tomsk, 634050



Yu. B. Dorofeeva
Siberian State Medical University (SSMU)
Russian Federation

Junior Researcher, Central Research Laboratory; Assistant Professor, Biology and Genetics Department,

2, Moscow Trakt, Tomsk, 634050



O. P. Ikkert
Siberian State Medical University (SSMU); National Research Tomsk State University
Russian Federation

PhD, Junior Researcher, Central Research Laboratory, 2, Moscow Trakt, Tomsk, 634050;

Senior Lecturer, Engineering School of New Manufacturing Technologies, The Scientific and Educational Center named after N.M. Kizhner, 36, Lenin Ave., 634050



M. A. Titova
Siberian State Medical University (SSMU)
Russian Federation

PhD, Associate Professor, Neurology and Neurosurgery Department,

2, Moscow Trakt, Tomsk, 634050



Yu. S. Mironova
Siberian State Medical University (SSMU)
Russian Federation

Post-Graduate Student, Neurology and Neurosurgery Department,

2, Moscow Trakt, Tomsk, 634050



A. E. Sazonov
Siberian State Medical University (SSMU)
Russian Federation

DM, Chief Researcher, Central Research Laboratory,

2, Moscow Trakt, Tomsk, 634050



M. R. Karpova
Siberian State Medical University (SSMU)
Russian Federation

DM, Professor, Head of the Microbiology and Virusology Department,

2, Moscow Trakt, Tomsk, 634050



References

1. Goetze O., Wieczorek J., Mueller T., Przuntek H., Schmidt W.E., Woitalla D. Impaired gastric emptying of a solid test meal in patients with Parkinson’s disease using 13C-sodium octanoate breath test. Neuroscience Letters. 2005; 375 (3): 170–173. DOI: 10.1016/j.neulet.2004.11.007.

2. Braak H., Ghebremedhin E., Rьb U., Bratzke H., Del Tredici K. Stages in the development of Parkinson’s disease-related pathology. Cell and Tissue Research. 2004; 318 (1): 121–134. DOI: 10.1007/s00441-004-0956-9.

3. Patrascu O., Beguet-Crespel F., Marinelli L., Le Chatelier E., Abraham A.L., Leclerc M., Klopp C., Terrapon N., Henrissat B., Blottiиre H.M., Dorй J. A fibrolytic potential in the human ileum mucosal microbiota revealed by functional metagenomic. Scientific Reports. 2017; 7: 40248. DOI: 10.1038/srep40248.

4. Fischbach M.A., Segre J.A. Signaling in host-associated microbial communities. Cell. 2016; 164 (6): 1288–1300. DOI: 10.1016/j.cell.2016.02.037.

5. Stiemsma L.T., Reynolds L.A., Turvey S.E., Finlay B.B. The hygiene hypothesis: current perspectives and future therapies. ImmunoTargets and Therapy. 2015; 4: 143. DOI: 10.2147/ITT.S61528.

6. Li J., Zhao F., Wang Y., Chen J., Tao J., Tian G., Wu S., Liu W., Cui Q., Geng B., Zhang W. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017; 5 (1): 14. DOI: 10.1186/s40168-016-0222-x.

7. Unger M.M., Mцller J.C., Mankel K., Eggert K.M., Bohne K., Bodden M., Stiasny-Kolster K., Kann P.H., Mayer G., Tebbe J.J., Oertel W.H. Postprandial ghrelin response is reduced in patients with Parkinson’s disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson’s disease? Journal of Neurology. 2011; 258 (6): 982–990. DOI: 10.1007/s00415-010-5864-1.

8. Hill-Burns E.M., Debelius J.W., Morton J.T., Wissemann W.T., Lewis M.R., Wallen Z.D., Peddada S.D., Factor S.A., Molho E., Zabetian C.P., Knight R. Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome. Movement Disorders. 2017; 32 (5): 739–749.

9. Scheperjans F., Aho V., Pereira P.A., Koskinen K., Paulin L., Pekkonen E., Haapaniemi E., Kaakkola S., Eerola-Rautio J., Pohja M., Kinnunen E. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Movement Disorders. 2015 March 1; 30 (3): 350–358. DOI: 10.1002/mds.26069.

10. Keshavarzian A., Green S.J., Engen P.A., Voigt R.M., Naqib A., Forsyth C.B., Mutlu E., Shannon K.M. Colonic bacterial composition in Parkinson’s disease. Movement Disorders. 2015; 30 (10): 1351–1360. DOI: 10.1002/mds.26307.

11. Hopfner F., Kьnstner A., Mьller S.H., Kьnzel S., Zeuner K.E., Margraf N.G., Deuschl G., Baines J.F., Kuhlenbдumer G. Gut microbiota in Parkinson disease in a northern German cohort. Brain Research. 2017; 1667: 41–45. DOI: 10.1016/j.brainres.2017.04.019.

12. Bedarf J.R., Hildebrand F., Coelho L.P., Sunagawa S., Bahram M., Goeser F., Bork P., Wullner D.U. Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-naпve Parkinson’s disease patients. Genome Medicine. 2017; 9 (1): 39. DOI: 10.1186/s13073-017-0428-y.

13. Tyakht A.V., Kostryukova E.S., Popenko A.S., Belenikin M.S., Pavlenko A.V., Larin A.K., Karpova I.Y., Selezneva O.V., Semashko T.A., Ospanova E.A., Babenko V.V. Human gut microbiota community structures in urban and rural populations in Russia. Nature Communications. 2013; 4: 2469. DOI: 10.1038/ncomms3469.

14. Dobbin Kevin K., Simon Richard M. Optimally splitting cases for training and testing high dimensional classifiers. BMC Medical Genomics. 2011; 4: 31. DOI: 10.1186/1755-8794-4-31.

15. Petrov V.A., Saltykova I.V., Zhukova I.A., Alifirova V.M., Zhukova N.G., Dorofeeva Y.B., Tyakht A.V., Kovarsky B.A., Alekseev D.G., Kostryukova E.S., Mironova Y.S. Analysis of gut microbiota in patients with Parkinson’s disease. Bulletin of Experimental Biology and Medicine. 2017; 162 (6): 734–737 (in Russ.).

16. Petrov V.A., Alifirova V.M., Saltykova I.V., Zhukova I.A., Zhukova N.G., Dorofeeva Yu.B., Tyakht A.V., Altukhov I.A., Kostryukova E.S., Titova M.A., Mironova Yu.S., Izhboldina O.P., Nikitina M.A., Perevozchikova T.V., Fait E.A., Sazonov A.E. Comparison study of gut microbiota in case of Parkinson’s disease and other neurological disorders. Bulletin of Siberian Medicine. 2016; 15 (5): 113–125 (in Russ.). DOI: 10.20538/1682-0363-2016-5-113-125.

17. Caporaso J.G., Kuczynski J., Stombaugh J., Bittinger K., Bushman F.D., Costello E.K., Fierer N., Pena A.G., Goodrich J.K., Gordon J.I., Huttley G.A. QIIME allows analysis of high-throughput community sequencing data. Nature Methods. 2010; 7 (5): 335–336. DOI: 10.1038/nmeth.f.303.

18. Ritari J., Salojarvi J., Lahti L., de Vos W.M. Improved taxonomic assignment of human intestinal 16S rRNA sequences by a dedicated reference database. BMC Genomics. 2015; 16: 1056. DOI: 10.1186/s12864-015-2265-y.

19. DeSantis T.Z., Hugenholtz P., Larsen N., Rojas M., Brodie E.L., Keller K., Huber T., Dalevi D., Hu P., Andersen G.L. Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Applied and Environmental Microbiology. 2006; 72 (7): 5069–5072. DOI: 10.1128/AEM.03006-05.

20. R Core Team (2016). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL: https://www.R-project.org.

21. Lozupone C., Knight R. UniFrac: a new phylogenetic method for comparing microbial communities. Applied and Environmental Microbiology. 2005 Dec.; 71 (12):

22. –8235. DOI: 10.1128/AEM.71.12.8228-8235.2005.

23. Paulson J.N., Stine O.C., Bravo H.C., Pop M. Differential abundance analysis for microbial marker-gene surveys. Nature Methods. 2013; 10 (12): 1200–1202. DOI: 10.1038/nmeth.2658.

24. Oksanen J., Blanchet F.G., Kindt R., Legendre P., Minchin P.R., O’hara R.B., Simpson G.L., Solymos P., Stevens M.H., Wagner H., Oksanen M.J. Package ‘vegan’. Community Ecology Package, version. 2013; 2 (9): 1–295.

25. Kuhn M. Caret package. Journal of Statistical Software. 2008; 28 (5): 1–26.

26. Braak H., de Vos R.A., Bohl J., Del Tredici K. Gastric a-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neuroscience Letters. 2006; 396 (1): 67–72. DOI: 10.1016/j.neulet.2005.11.012.

27. Pasolli E., Truong D.T., Malik F., Waldron L., Segata N. Machine learning meta-analysis of large metagenomics datasets: tools and biological insights. PLoS Computational Biology. 2016; 12 (7): e1004977. DOI: 10.1371/journal.pcbi.1004977.

28. Hand D.J., Yu K. Idiot’s Bayes – not so stupid after all? International Statistical Review. 2001; 69 (3): 385–398. DOI: 10.1111/j.1751-5823.2001.tb00465.x.


Review

For citations:


Petrov V.A., Alifirova V.M., Saltykova I.V., Zhukova I.A., Zhukova N.G., Dorofeeva Yu.B., Ikkert O.P., Titova M.A., Mironova Yu.S., Sazonov A.E., Karpova M.R. Diagnostic potential of gut microbiota in Parkinson’s disease. Bulletin of Siberian Medicine. 2019;18(4):92-101. https://doi.org/10.20538/1682-0363-2019-4-92-101

Views: 862


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)