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Altered gut microbiota in patients with idiopathic Parkinson’s disease: an age–sex matched case–control study

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Abstract

Objective

The investigations related to how gut microbiota changes the brain–gut axis in idiopathic Parkinson’s disease (PD) attract growing interest. We aimed to determine whether gut microbiota is altered in PD patients and whether non-motor symptoms of PD and disease duration had any relation with alterations of microbiota profiles among patients.

Methods

Microbial taxa in stool samples obtained from 84 subjects (42-PD patients and 42-healthy spouses) were analyzed using 16S rRNA amplicon-sequencing.

Results

We observed a significant decrease of Firmicutes and a significant increase of Verrucomicrobiota at the phylum level. At the family level, Lactobacillaceae and Akkermansiaceae were significantly increased and Coriobacteriales Incertae Sedis were significantly decreased in the PD patients compared to their healthy spouses. Genus level comparison inferred significant increase in abundance only in Lactobacillus while the abundance of Lachnospiraceae ND3007 group, Tyzzerella, Fusicatenibacter, Eubacterium hallii group and Ruminococcus gauvreauii group were all decreased. We determined that the abundance of Prevotella genus decreased, but not significantly in PD patients. In addition, we found differences in microbiota composition between patients with and without non-motor symptoms.

Conclusion

We observed differences in gut microbiota composition between PD patients and their healthy spouses. Our findings suggest that disease duration influenced microbiota composition, which in turn influenced development of non-motor symptoms in PD. This study is the first in terms of both gut microbiota research in Turkish PD patients and the probable effect of microbiota on non-motor symptoms of PD.

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Data availability statement

All relevant data are within the manuscript.

References

  1. Hughes AJ, Daniel SE, Kilford L (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181–184. https://doi.org/10.1136/jnnp.55.3.181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Malek N, Swallow D, Grosset KA et al (2014) Alpha-synuclein in peripheral tissues and body fluids as a biomarker for Parkinson’s disease—a systematic review. Acta Neurol Scand 130:59–72. https://doi.org/10.1111/ane.12247

    Article  CAS  PubMed  Google Scholar 

  3. Abbott RD, Petrovitch H, Masaki KH (2001) Frequency of bowel movements and the future risk of Parkinson’s disease. Neurology 57:456–462. https://doi.org/10.1212/wnl.57.3.456

    Article  CAS  PubMed  Google Scholar 

  4. Shannon KM, Keshavarzian A, Mutlu E et al (2012) Alpha-synuclein in colonic submucosa in early untreated Parkinson’s disease. Mov Disord 27:709–715. https://doi.org/10.1002/mds.23838

    Article  PubMed  Google Scholar 

  5. Klingelhoefer L, Reichmann H (2015) Pathogenesis of Parkinson disease—the gut-brain axis and environmental factors. Nat Rev Neurol 11(11):625–636. https://doi.org/10.1038/nrneurol.2015.197

    Article  CAS  PubMed  Google Scholar 

  6. Braak H, de Vos RA, Bohl J, Del Tredici K (2006) Gastric alpha-synuclein immunoreactive inclusions in Meissner’s and Auerbach’s plexuses in cases staged for Parkinson’s disease-related brain pathology. Neurosci Lett 396:67–72. https://doi.org/10.1016/j.neulet.2005.11.012

    Article  CAS  PubMed  Google Scholar 

  7. Menozzi E, Macnaughtan J, Schapira AHV (2021) The gut-brain axis and Parkinson disease: clinical and pathogenetic relevance. Ann Med 53:611–625. https://doi.org/10.1080/07853890.2021.1890330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Keshavarzian A, Green SJ, Engen PA, Voigt RM, Naqib A, Forsyth CB, Mutlu E, Shannon KM (2015) Colonic bacterial composition in Parkinson’s disease. Mov Disord 30:1351–1360. https://doi.org/10.1002/mds.26307

    Article  CAS  PubMed  Google Scholar 

  9. Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P (2015) Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 30(3):350–358. https://doi.org/10.1002/mds.26069

    Article  PubMed  Google Scholar 

  10. Sender R, Fuchs S, Milo R (2016) Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164(3):337–340. https://doi.org/10.1016/j.cell.2016.01.013

    Article  CAS  PubMed  Google Scholar 

  11. Qin J, Li R, Raes J, Arumugam M et al (2010) A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464(7285):59–65. https://doi.org/10.1038/nature08821

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Clarke G, Grenham S, Scully P et al (2013) The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18:666–673. https://doi.org/10.1038/mp.2012.77

    Article  CAS  PubMed  Google Scholar 

  13. Shen T, Yue Y, He T, Huang C, Qu B, Lv W, Lai H-Y (2021) The association between the gut microbiota and Parkinson’s disease, a meta-analysis. Front Aging Neurosci 13:636545. https://doi.org/10.3389/fnagi.2021.636545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Poewe WH, Wenning GK (1998) The natural history of Parkinson’s disease. Ann Neurol 44(3 Suppl 1):S1-9. https://doi.org/10.1002/ana.410440703

    Article  CAS  PubMed  Google Scholar 

  15. Stiasny-Kolster K, Mayer G, Schäfer S, Möller JC, Heinzel-Gutenbrunner M, Oertel WH (2007) The REM sleep behavior disorder screening questionnaire—a new diagnostic instrument. Mov Disord 22(16):2386–2393. https://doi.org/10.1002/mds.21740

    Article  PubMed  Google Scholar 

  16. Comert IT, Pelin Z, Aricak T, Yapan S (2016) Validation of the Turkish version of the rapid eye movement sleep behavior disorder questionnaire. Behav Neurol. https://doi.org/10.1155/2016/8341651

    Article  Google Scholar 

  17. Bolyen E, Rideout JR, Dillon MR et al (2019) Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol 37:852–857. https://doi.org/10.1038/s41587-019-0209-9. (Erratum in: Nat Biotechnol 2019; 37(9): 1091)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Amir A, McDonald D, Navas-Molina JA et al (2017) Deblur rapidly resolves single-nucleotide community sequence patterns. Msystems 2(2):e00191-16. https://doi.org/10.1128/mSystems.00191-16

    Article  PubMed  PubMed Central  Google Scholar 

  19. Morgan XC, Tickle TL, Sokol H et al (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol 13(9):R79. https://doi.org/10.1186/gb-2012-13-9-r79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cilia R, Piatti M, Cereda E, Bolliri C, Caronni S, Ferri V, Cassani E, Bonvegna S, Ferrarese C, Zecchinelli AL, Barichella M, Pezzoli G (2021) Does gut microbiota influence the course of Parkinson’s disease? A 3-year prospective exploratory study in de novo patients. J Parkinsons Dis 11(1):159–170. https://doi.org/10.3233/JPD-202297

    Article  CAS  PubMed  Google Scholar 

  21. Lin A, Zheng W, He Y, Tang W, Wei X, He R, Huang W, Su Y, Huang Y, Zhou H, Xie H (2018) Gut microbiota in patients with Parkinson’s disease in southern China. Parkinsonism Relat Disord 53:82–88. https://doi.org/10.1016/j.parkreldis.2018.05.007

    Article  PubMed  Google Scholar 

  22. Zhang Y, Guo C, Ma G, Sang M, Chen F, Wang P (2020) Altered gut microbiota in Parkinson’s disease patients/healthy spouses and its association with clinical features. Parkinsonism Relat Disord 81:84–88. https://doi.org/10.1016/j.parkreldis.2020.10.034

    Article  PubMed  Google Scholar 

  23. Li F, Wang P, Chen Z, Sui X, Xie X, Zhang J (2019) Alteration of the fecal microbiota in North-Eastern Han Chinese population with sporadic Parkinson’s disease. Neurosci Lett 707:134297. https://doi.org/10.1016/j.neulet.2019.134297

    Article  CAS  PubMed  Google Scholar 

  24. Hill-Burns EM, Debelius JW, Morton JT et al (2017) Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome. Mov Disord 32(5):739–749. https://doi.org/10.1002/mds.26942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jin M, Li J, Liu F, Lyu N, Wang K, Wang L, Liang S, Tao H, Zhu B, Alkasir R (2019) Analysis of the gut microflora in patients with Parkinson’s disease. Front Neurosci 13:1184. https://doi.org/10.3389/fnins.2019.01184

    Article  PubMed  PubMed Central  Google Scholar 

  26. Pietrucci D, Cerroni R, Unida V, Farcomeni A, Pierantozzi M, Mercuri NB, Biocca S, Stefani A, Desideri A (2019) Dysbiosis of gut microbiota in a selected population of Parkinson’s patients. Parkinsonism Relat Disord 65:124–130. https://doi.org/10.1016/j.parkreldis.2019.06.003

    Article  PubMed  Google Scholar 

  27. Hopfner F, Künstner A, Müller SH, Künzel S, Zeuner KE, Margraf NG, Deuschl G, Baines JF, Kuhlenbäumer G (2017) Gut microbiota in Parkinson disease in a northern German cohort. Brain Res 1667:41–45. https://doi.org/10.1016/j.brainres.2017.04.019

    Article  CAS  PubMed  Google Scholar 

  28. Forsyth CB, Shannon KM, Kordower JH et al (2011) Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson’s disease. PLoS ONE 6(12):e28032. https://doi.org/10.1371/journal.pone.0028032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hasegawa S, Goto S, Tsuji H et al (2015) Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson’s disease. PLoS ONE 10(11):e0142164. https://doi.org/10.1371/journal.pone.0142164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Heintz-Buschart A, Pandey U, Wicke T, Sixel-Döring F, Janzen A, Sittig-Wiegand E, Trenkwalder C, Oertel WH, Mollenhauer B, Wilmes P (2018) The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder. Mov Disord 33(1):88–98. https://doi.org/10.1002/mds.27105

    Article  CAS  PubMed  Google Scholar 

  31. Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, Faßbender K, Schwiertz A, Schäfer KH (2016) Short chain fatty acids and gut microbiota differ between patients with Parkinson’s disease and age-matched controls. Parkinsonism Relat Disord 32:66–72. https://doi.org/10.1016/j.parkreldis.2016.08.019

    Article  PubMed  Google Scholar 

  32. Derrien M, Vaughan EE, Plugge CM, de Vos WM (2004) Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. Int J Syst Evol Microbiol 54(Pt 5):1469–1476. https://doi.org/10.1099/ijs.0.02873-0

    Article  CAS  PubMed  Google Scholar 

  33. Nishiwaki H, Ito M, Ishida T, Hamaguchi T, Maeda T, Kashihara K, Tsuboi Y, Ueyama J, Shimamura T, Mori H, Kurokawa K, Katsuno M, Hirayama M, Ohno K (2020) Meta-analysis of gut dysbiosis in Parkinson’s disease. Mov Disord 35(9):1626–1635. https://doi.org/10.1002/mds.28119

    Article  CAS  PubMed  Google Scholar 

  34. Arumugam M, Raes J, Pelletier E et al (2011) Enterotypes of the human gut microbiome. Nature 473:174–180. https://doi.org/10.1038/nature09944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. De Vadder F, Kovatcheva-Datchary P, Goncalves D, Vinera J, Zitoun C, Duchampt A, Bäckhed F, Mithieux G (2014) Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 156:84–96. https://doi.org/10.1016/j.cell.2013.12.016

    Article  CAS  PubMed  Google Scholar 

  36. Cryan JF, O’Riordan KJ, Cowan CSM et al (2019) The microbiota-gut-brain axis. Physiol Rev 99:1877–2013. https://doi.org/10.1152/physrev.00018.2018

    Article  CAS  PubMed  Google Scholar 

  37. Andrews ZB, Erion D, Beiler R et al (2009) Ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. J Neurosci 29(45):14057–14065. https://doi.org/10.1523/jneurosci.3890-09.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Haehner A, Boesveldt S, Berendse HW et al (2009) Prevalence of smell loss in Parkinson’s disease-a multicenter study. Parkinsonism Relat Disord 15:490–494. https://doi.org/10.1016/j.parkreldis.2008.12.005

    Article  CAS  PubMed  Google Scholar 

  39. Noyce AJ, Bestwick JP, Silveira-Moriyama L, Hawkes CH, Giovannoni G, Lees AJ, Schrag A (2012) Meta-analysis of early nonmotor features and risk factors for Parkinson disease. Ann Neurol 72:893–901. https://doi.org/10.1002/ana.23687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Driver-Dunckley E, Adler CH, Hentz JG, Dugger BN, Shill HA, Caviness JN, Sabbagh MN, Beach TG (2014) Arizona Parkinson Disease Consortium, Olfactory dysfunction in incidental Lewy body disease and Parkinson’s disease. Parkinsonism Relat Disord 20(11):1260–1262. https://doi.org/10.1016/j.parkreldis.2014.08.006

    Article  PubMed  PubMed Central  Google Scholar 

  41. Lubomski M, Xu X, Holmes AJ, Muller S, Yang JYH, Davis RL, Sue CM (2022) Nutritional intake and gut microbiome composition predict Parkinson’s disease. Front Aging Neurosci 14:881872. https://doi.org/10.3389/fnagi.2022.881872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhu L, Liu W, Alkhouri R, Baker RD, Bard JE, Quigley EM, Baker SS (2014) Structural changes in the gut microbiome of constipated patients. Physiol Genomics 46(18):679–686. https://doi.org/10.1152/physiolgenomics.00082.2014

    Article  CAS  PubMed  Google Scholar 

  43. Henke MT, Kenny DJ, Cassilly CD, Vlamakis H, Xavier RJ, Clardy J (2019) Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide. Proc Natl Acad Sci USA 116(26):12672–12677. https://doi.org/10.1073/pnas.1904099116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Vascellari S, Palmas V, Melis M et al (2020) Gut microbiota and metabolome alterations associated with Parkinson’s Disease. MSystems. https://doi.org/10.1128/MSYSTEMS.00561-20

    Article  PubMed  PubMed Central  Google Scholar 

  45. Gómez-Esteban JC, Zarranz JJ, Tijero B et al (2007) Restless legs syndrome in Parkinson’s disease. Mov Disord 22:1912–1916. https://doi.org/10.1002/mds.21624

    Article  PubMed  Google Scholar 

  46. Blum DJ, During E, Barwick F, Davidenko P, Zeitzer JM (2019) Restless leg syndrome: does it start with a gut feeling? Sleep 42(1):A4. https://doi.org/10.1093/sleep/zsz067.008

    Article  Google Scholar 

  47. Fasano A, Bove F, Gabrielli M et al (2013) The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord 28(9):1241–1249. https://doi.org/10.1002/mds.25522

    Article  CAS  PubMed  Google Scholar 

  48. Morais LH, Schreiber HL, Mazmanian SK (2021) The gut microbiota–brain axis in behaviour and brain disorders. Nat Rev Microbiol 19:241–255. https://doi.org/10.1038/s41579-020-00460-0

    Article  CAS  PubMed  Google Scholar 

  49. Li X, Chen LM, Kumar G et al (2022) Therapeutic interventions of gut-brain axis as novel strategies for treatment of alcohol use disorder associated cognitive and mood dysfunction. Front Neurosci 16:820106. https://doi.org/10.3389/fnins.2022.820106

    Article  PubMed  PubMed Central  Google Scholar 

  50. Collins S, Surette M, Bercik P (2012) The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 10:735–742. https://doi.org/10.1038/nrmicro2876

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the patients and their family members and TUBITAK (The Scientific and Technological Research Council of Turkiye) for supporting this study.

Funding

The study was supported by the grant from the Turkish Scientific and Technical Council (TÜBITAK-118S704) and by the Bezmialem Vakif University Scientific Research Found (6.2017/53).

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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by GBY, OG, ZCK, BS, and BE. The data analysis and writing the first draft were performed by GBY, ZCK, IK, and OA. All authors read and approved the final manuscript.

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Correspondence to Gulsen Babacan Yildiz.

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The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Approval was obtained from the Bezmialem Vakıf University Ethics Committee (approval no.: 12/27) and the research was carried out in accordance with the declaration of Helsinki.

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A freely given, written informed consent was obtained from all individual participants included in the study.

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Babacan Yildiz, G., Kayacan, Z.C., Karacan, I. et al. Altered gut microbiota in patients with idiopathic Parkinson’s disease: an age–sex matched case–control study. Acta Neurol Belg 123, 999–1009 (2023). https://doi.org/10.1007/s13760-023-02195-0

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