Science China Life Sciences

, Volume 60, Issue 11, pp 1223–1233 | Cite as

Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features

  • Wei Li
  • Xiaoli Wu
  • Xu Hu
  • Tao Wang
  • Shan Liang
  • Yunfeng Duan
  • Feng JinEmail author
  • Bin QinEmail author
Research Paper


The aim of this study was to compare the structure of gut microbiota in Parkinson’s disease (PD) patients and healthy controls; and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia (P=0.018), Faecalibacterium (P=0.048) and Ruminococcus (P=0.019) were significantly decreased in PD compared to healthy controls. The putative pathobionts from the genera Escherichia-Shigella (P=0.038), Streptococcus (P=0.01), Proteus (P=0.022), and Enterococcus (P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.


microbiome α-synuclein gastrointestinal dysfunction gut-brain-axis 16S rRNA sequencing short chain fatty acids 


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This work was supported by Future Life Sciences International Ltd. (NSBJ01032014,

Supplementary material

11427_2016_9001_MOESM1_ESM.pdf (65 kb)
Rarefaction curves of Shannon index.
11427_2016_9001_MOESM2_ESM.pdf (474 kb)
Family level comparison.
11427_2016_9001_MOESM3_ESM.pdf (264 kb)
The heatmap based on the relative abundance of top 65 abundant genera.
11427_2016_9001_MOESM4_ESM.pdf (58 kb)
Significantly different genera between PD and HC groups
11427_2016_9001_MOESM5_ESM.pdf (34 kb)
Demographic characteristics of three groups
11427_2016_9001_MOESM6_ESM.pdf (60 kb)
Summary of clinical information between PD and HC groups


  1. Abell, G.C.J., Cooke, C.M., Bennett, C.N., Conlon, M.A., and McOrist, A.L. (2008). Phylotypes related to Ruminococcus bromii are abundant in the large bowel of humans and increase in response to a diet high in resistant starch. FEMS Microbiol Ecol 66, 505–515.CrossRefPubMedGoogle Scholar
  2. Adams, J.B., Johansen, L.J., Powell, L.D., Quig, D., and Rubin, R.A. (2011). Gastrointestinal flora and gastrointestinal status in children with autism-comparisons to typical children and correlation with autism severity. BMC Gastroenterol 11, 22.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Agachan, F., Chen, T., Pfeifer, J., Reissman, P., and Wexner, S.D. (1996). A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum 39, 681–685.CrossRefPubMedGoogle Scholar
  4. Bercik, P., Denou, E., Collins, J., Jackson, W., Lu, J., Jury, J., Deng, Y., Blennerhassett, P., Macri, J., McCoy, K.D., Verdu, E.F., and Collins, S.M. (2011). The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141, 599–609.e3.CrossRefPubMedGoogle Scholar
  5. Bolger, A.M., Lohse, M., and Usadel, B. (2014). Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Braak, H., Ghebremedhin, E., Rüb, U., Bratzke, H., and Del Tredici, K. (2004). Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res 318, 121–134.CrossRefPubMedGoogle Scholar
  7. Braak, H., Rüb, U., Gai, W.P., and Del Tredici, K. (2003). Idiopathic Parkinson’s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J Neural Transm (Vienna) 110, 517–536.CrossRefGoogle Scholar
  8. Bridgewater, F.A., Morgan, R.S., Rowson, K.E., and Wright, G.P. (1955). The Neurotoxin of Shigella shigae: morphological and functional lesions produced in the central nervous system of rabbits. Br J Exp Pathol 36, 447–453.Google Scholar
  9. Brugman, S., Klatter, F.A., Visser, J.T.J., Wildeboer-Veloo, A.C.M., Harmsen, H.J.M., Rozing, J., and Bos, N.A. (2006). Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes? Diabetologia 49, 2105–2108.CrossRefPubMedGoogle Scholar
  10. Cavanagh, J., Howard, J., and Whitby, J. (1956). The neurotoxin of Shigella shigae. A comparative study of the effects produced in various laboratory animals. Br J Exp Pathol 37, 272.PubMedGoogle Scholar
  11. Cersosimo, M.G., Raina, G.B., Pecci, C., Pellene, A., Calandra, C.R., Gutiérrez, C., Micheli, F.E., and Benarroch, E.E. (2013). Gastrointestinal manifestations in Parkinson’s disease: prevalence and occurrence before motor symptoms. J Neurol 260, 1332–1338.CrossRefPubMedGoogle Scholar
  12. Chaudhuri, K.R., Healy, D.G., and Schapira, A.H. (2006). Non-motor symptoms of Parkinson’s disease: diagnosis and management. Lancet Neurol 5, 235–245.CrossRefPubMedGoogle Scholar
  13. Chen, Y., Yang, F., Lu, H., Wang, B., Chen, Y., Lei, D., Wang, Y., Zhu, B., and Li, L. (2011). Characterization of fecal microbial communities in patients with liver cirrhosis. Hepatology 54, 562–572.CrossRefPubMedGoogle Scholar
  14. Cho, Y., Turner, N.D., Davidson, L.A., Chapkin, R.S., Carroll, R.J., and Lupton, J.R. (2014). Colon cancer cell apoptosis is induced by combined exposure to the n-3 fatty acid docosahexaenoic acid and butyrate through promoter methylation. Exp Biol Med 239, 302–310.CrossRefGoogle Scholar
  15. Collins, S.M., and Bercik, P. (2009). The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 136, 2003–2014.CrossRefPubMedGoogle Scholar
  16. Cryan, J.F., and Dinan, T.G. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci 13, 701–712.CrossRefPubMedGoogle Scholar
  17. de Lau, L.M., and Breteler, M.M. (2006). Epidemiology of Parkinson’s disease. Lancet Neurol 5, 525–535.CrossRefPubMedGoogle Scholar
  18. Dobbs, R.J., Charlett, A., Dobbs, S.M., Weller, C., A Ibrahim, M.A., Iguodala, O., Smee, C., Plant, J.M., Lawson, A.J., Taylor, D., and Bjarnason, I. (2012). Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study. Gut Pathog 4, 12.CrossRefPubMedGoogle Scholar
  19. Dobbs, R.J., Charlett, A., Purkiss, A.G., Dobbs, S.M., Weller, C., and Peterson, D.W. (1999). Association of circulating TNF-a and IL-6 with ageing and parkinsonism. Acta Neurol Scand 100, 34–41CrossRefPubMedGoogle Scholar
  20. Dobbs, S.M., Dobbs, R.J., Weller, C., Charlett, A., Augustin, A., Taylor, D., Ibrahim, M.A.A., and Bjarnason, I. (2016). Peripheral aetiopathogenic drivers and mediators of Parkinson’s disease and co-morbidities: role of gastrointestinal microbiota. J Neurovirol 22, 22–32.CrossRefPubMedGoogle Scholar
  21. Endimiani, A., Luzzaro, F., Brigante, G., Perilli, M., Lombardi, G., Amicosante, G., Roßsolini, G.M., and Toniolo, A. (2005). Proteus mirabilis bloodstream infections: risk factors and treatment outcome related to the expression of extended-spectrum ß-lactamases. Antimicrob Agents Chemother 49, 2598–2605.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Erkkilä, A., de Mello, V.D.F., Risérus, U., and Laaksonen, D.E. (2008). Dietary fatty acids and cardiovascular disease: an epidemiological approach. Prog Lipid Res 47, 172–187.CrossRefPubMedGoogle Scholar
  23. Fasano, A., Bove, F., Gabrielli, M., Petracca, M., Zocco, M.A., Ragazzoni, E., Barbaro, F., Piano, C., Fortuna, S., Tortora, A., Di Giacopo, R., Campanale, M., Gigante, G., Lauritano, E.C., Navarra, P., Marconi, S., Gasbarrini, A., and Bentivoglio, A.R. (2013). The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord 28, 1241–1249.CrossRefPubMedGoogle Scholar
  24. Fasano, A., Visanji, N.P., Liu, L.W.C., Lang, A.E., and Pfeiffer, R.F. (2015). Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol 14, 625–639.CrossRefPubMedGoogle Scholar
  25. Felice, V.D., Quigley, E.M., Sullivan, A.M., O’Keeffe, G.W., and O’Mahony, S.M. (2016). Microbiota-gut-brain signalling in Parkinson’s disease: implications for non-motor symptoms. Parkinsonism Relat Disord 27, 1–8.CrossRefPubMedGoogle Scholar
  26. Goetz, C.G., Poewe, W., Rascol, O., Sampaio, C., Stebbins, G.T., Counsell, C., Giladi, N., Holloway, R.G., Moore, C.G., Wenning, G.K., Yahr, M.D., Seidl, L., and Seidl, L. (2004). Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations The Movement Disorder Society Task Force on rating scales for Parkinson’s disease. Mov Disord 19, 1020–1028.CrossRefPubMedGoogle Scholar
  27. Hamilton, M. (1959). The assessment of anxiety states by rating. Brit J Med Psychol 32, 50–55.CrossRefPubMedGoogle Scholar
  28. Hamilton, M. (1960). A rating scale for depression. J Neurol Neurosurg Psychiatry 23, 56–62.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Heetun, Z.S., and Quigley, E.M.M. (2012). Gastroparesis and Parkinson’s disease: a systematic review. Parkinsonism Relat Disord 18, 433–440.CrossRefPubMedGoogle Scholar
  30. Hu, X., Wang, T., and Jin, F. (2016). Alzheimer’s disease and gut microbiota. Sci China Life Sci 59, 1006–1023.CrossRefPubMedGoogle Scholar
  31. Hughes, A.J., Daniel, S.E., Kilford, L., and Lees, A.J. (1992). Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55, 181–184.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Huycke, M.M., Abrams, V., and Moore, D.R. (2002). Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 23, 529–536.CrossRefPubMedGoogle Scholar
  33. Jiang, H., Ling, Z., Zhang, Y., Mao, H., Ma, Z., Yin, Y., Wang, W., Tang, W., Tan, Z., Shi, J., Li, L., and Ruan, B. (2015). Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun 48, 186–194.CrossRefPubMedGoogle Scholar
  34. Keshavarzian, A., Green, S.J., Engen, P.A., Voigt, R.M., Naqib, A., Forsyth, C.B., Mutlu, E., and Shannon, K.M. (2015). Colonic bacterial composition in Parkinson’s disease. Mov Disord 30, 1351–1360.CrossRefPubMedGoogle Scholar
  35. Kozich, J.J., Westcott, S.L., Baxter, N.T., Highlander, S.K., and Schloss, P.D. (2013). Development of a dual-index sequencing strategy and curation pipeline for analyzing amplicon sequence data on the MiSeq Illumina sequencing platform. Appl Environ Microbiol 79, 5112–5120.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Lang, A.E. (2011). A critical appraisal of the premotor symptoms of Parkinson’s disease: potential usefulness in early diagnosis and design of neuroprotective trials. Mov Disord 26, 775–783.CrossRefPubMedGoogle Scholar
  37. Leitch, E.C.M.W., Walker, A.W., Duncan, S.H., Holtrop, G., and Flint, H.J. (2007). Selective colonization of insoluble substrates by human faecal bacteria. Environ Microbiol 9, 667–679.CrossRefPubMedGoogle Scholar
  38. Macpherson, A.J., and Harris, N.L. (2004). Opinion: interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4, 478–485.CrossRefPubMedGoogle Scholar
  39. Movement Disorder Society Task Force on Rating Scales for Parkinson’s Disease. (2003). The Unified Parkinson’s Disease Rating Scale (UPDRS): status and recommendations. Mov Disord 18, 738–750.CrossRefGoogle Scholar
  40. Mulak, A., and Bonaz, B. (2015). Brain-gut-microbiota axis in Parkinson’s disease. World J Gastroenterol 21, 10609–10620.CrossRefPubMedPubMedCentralGoogle Scholar
  41. Nakano, K., Mizuno, T., Sowa, Y., Orita, T., Yoshino, T., Okuyama, Y., Fujita, T., Ohtani-Fujita, N., Matsukawa, Y., Tokino, T., Yamagishi, H., Oka, T., Nomura, H., and Sakai, T. (1997). Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line. J Biol Chem 272, 22199–22206.CrossRefPubMedGoogle Scholar
  42. Nicholson, J.K., Holmes, E., and Wilson, I.D. (2005). Opinion: gut microorganisms, mammalian metabolism and personalized health care. Nat Rev Micro 3, 431–438.CrossRefGoogle Scholar
  43. Ottman, N., Smidt, H., de Vos, W.M., and Belzer, C. (2012). The function of our microbiota: who is out there and what do they do? Front Cell Inf Microbio 2, 104.CrossRefGoogle Scholar
  44. Parracho, H.M.R.T., Bingham, M.O., Gibson, G.R., and McCartney, A.L. (2005). Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol 54, 987–991.CrossRefPubMedGoogle Scholar
  45. Pfeiffer, R.F. (2011). Gastrointestinal dysfunction in Parkinson’s disease. Parkinsonism Relat Disord 17, 10–15.CrossRefPubMedGoogle Scholar
  46. Pruesse, E., Quast, C., Knittel, K., Fuchs, B.M., Ludwig, W., Peplies, J., and Glöckner, F.O. (2007). SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB. Nucleic Acids Res 35, 7188–7196.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Qin, N., Yang, F., Li, A., Prifti, E., Chen, Y., Shao, L., Guo, J., Le Chatelier, E., Yao, J., Wu, L., Zhou, J., Ni, S., Liu, L., Pons, N., Batto, J.M., Kennedy, S.P., Leonard, P., Yuan, C., Ding, W., Chen, Y., Hu, X., Zheng, B., Qian, G., Xu, W., Ehrlich, S.D., Zheng, S., and Li, L. (2014). Alterations of the human gut microbiome in liver cirrhosis. Nature 513, 59–64.CrossRefPubMedGoogle Scholar
  48. Rayner, C.K., and Horowitz, M. (2013). Physiology of the ageing gut. Curr Opin Clin Nutr Metab Care 16, 33–38.CrossRefPubMedGoogle Scholar
  49. Riordan, S.M., and Williams, R. (2006). The intestinal flora and bacterial infection in cirrhosis. J Hepatol 45, 744–757.CrossRefPubMedGoogle Scholar
  50. Schaffer, J.N., and Pearson, M.M. (2015). Proteus mirabilis and Urinary Tract Infections. Microbiol Spectr in press doi: 10.1128/microbiolspec.UTI-0017-2013.Google Scholar
  51. Scheperjans, F., Aho, V., Pereira, P.A.B., Koskinen, K., Paulin, L., Pekkonen, E., Haapaniemi, E., Kaakkola, S., Eerola-Rautio, J., Pohja, M., Kinnunen, E., Murros, K., and Auvinen, P. (2015). Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord 30, 350–358.CrossRefPubMedGoogle Scholar
  52. Scher, J.U., Sczesnak, A., Longman, R.S., Segata, N., Ubeda, C., Bielski, C., Rostron, T., Cerundolo, V., Pamer, E.G., Abramson, S.B., Huttenhower, C., and Littman, D.R. (2013). Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2, e01202.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Schloss, P.D., Westcott, S.L., Ryabin, T., Hall, J.R., Hartmann, M., Hollister, E.B., Lesniewski, R.A., Oakley, B.B., Parks, D.H., Robinson, C.J., Sahl, J.W., Stres, B., Thallinger, G.G., Van Horn, D.J., and Weber, C.F. (2009). Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 75, 7537–7541.CrossRefPubMedPubMedCentralGoogle Scholar
  54. Sjögren, Y.M., Jenmalm, M.C., Böttcher, M.F., Björkstén, B., and Sverremark-Ekström, E. (2009). Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clin Exp Allergy 39, 518–526.CrossRefPubMedGoogle Scholar
  55. Takahashi, K., Nishida, A., Fujimoto, T., Fujii, M., Shioya, M., Imaeda, H., Inatomi, O., Bamba, S., Sugimoto, M., and Andoh, A. (2016). Reduced abundance of butyrate-producing bacteria species in the fecal microbial community in Crohn’s disease. Digestion 93, 59–65.CrossRefPubMedGoogle Scholar
  56. Tan, A.H., Mahadeva, S., Thalha, A.M., Gibson, P.R., Kiew, C.K., Yeat, C.M., Ng, S.W., Ang, S.P., Chow, S.K., Tan, C.T., Yong, H.S., Marras, C., Fox, S.H., and Lim, S.Y. (2014). Small intestinal bacterial overgrowth in Parkinson’s disease. Parkinsonism Relat Disord 20, 535–540.CrossRefPubMedGoogle Scholar
  57. Topping, D.L., and Clifton, P.M. (2001). Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol Rev 81, 1031-1064.CrossRefPubMedGoogle Scholar
  58. Vinolo, M.A.R., Rodrigues, H.G., Nachbar, R.T., and Curi, R. (2011). Regulation of inflammation by short chain fatty acids. Nutrients 3, 858–876.CrossRefPubMedPubMedCentralGoogle Scholar
  59. Walker, A.W., Ince, J., Duncan, S.H., Webster, L.M., Holtrop, G., Ze, X., Brown, D., Stares, M.D., Scott, P., Bergerat, A., Louis, P., McIntosh, F., Johnstone, A.M., Lobley, G.E., Parkhill, J., and Flint, H.J. (2011). Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J 5, 220–230.CrossRefPubMedGoogle Scholar
  60. Wang, R.F., Cao, W.W., and Cerniglia, C.E. (1997). PCR detection of Ruminococcus spp. in human and animal faecal samples. Mol Cell Probes 11, 259–265.CrossRefPubMedGoogle Scholar
  61. Wang, T., Cai, G., Qiu, Y., Fei, N., Zhang, M., Pang, X., Jia, W., Cai, S., and Zhao, L. (2012). Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 6, 320–329.CrossRefPubMedGoogle Scholar
  62. White, J.R., Nagarajan, N., and Pop, M. (2009). Statistical methods for detecting differentially abundant features in clinical metagenomic samples. PLoS Comput Biol 5, e1000352.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Heidelberg 2017

Authors and Affiliations

  1. 1.Key Laboratory of Mental Health, Institute of PsychologyChinese Academy of SciencesBeijingChina
  2. 2.University of Chinese Academy of SciencesBeijingChina
  3. 3.Department of NeurologyBeijing HospitalBeijingChina

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