Neurochemical Research

, Volume 43, Issue 10, pp 1986–1999 | Cite as

Intestinal Pathology and Gut Microbiota Alterations in a Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Mouse Model of Parkinson’s Disease

  • Feng Lai
  • Rong Jiang
  • Wenjun Xie
  • Xinrong Liu
  • Yong Tang
  • Hong Xiao
  • Jieying Gao
  • Yan Jia
  • Qunhua Bai
Original Paper


Patients with Parkinson’s disease (PD) often have non-motor symptoms related to gastrointestinal (GI) dysfunction, such as constipation and delayed gastric emptying, which manifest prior to the motor symptoms of PD. Increasing evidence indicates that changes in the composition of the gut microbiota may be related to the pathogenesis of PD. However, it is unclear how GI dysfunction occurs and how gut microbial dysbiosis is caused. We investigated whether a neurotoxin model of PD induced by chronic low doses of MPTP is capable of reproducing the clinical intestinal pathology of PD, as well as whether gut microbial dysbiosis accompanies this pathology. C57BL/6 male mice were administered 18 mg/kg MPTP twice per week for 5 weeks via intraperitoneal injection. GI function was assessed by measuring the 1-h stool frequency and fecal water content; motor function was assessed by pole tests; and tyrosine hydroxylase and alpha-synuclein expression were analyzed. Furthermore, the inflammation, intestinal barrier and composition of the gut microbiota were measured. We found that MPTP caused GI dysfunction and intestinal pathology prior to motor dysfunction. The composition of the gut microbiota was changed; in particular, the change in the abundance of Lachnospiraceae, Erysipelotrichaceae, Prevotellaceae, Clostridiales, Erysipelotrichales and Proteobacteria was significant. These results indicate that a chronic low-dose MPTP model can be used to evaluate the progression of intestinal pathology and gut microbiota dysbiosis in the early stage of PD, which may provide new insights into the pathogenesis of PD.


Parkinson’s disease MPTP Intestinal pathology Gut microbiota 



The present study was supported by the Chongqing Yuzhong Nature Science Foundation of China (Grant No. 20160121).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11064_2018_2620_MOESM1_ESM.bmp (38.4 mb)
Fig. S1 Indexes of α-diversity including Sobs (a) and Simpson (b). (BMP 39361 KB)
11064_2018_2620_MOESM2_ESM.bmp (38.4 mb)
Fig. S2 Comparisons of the relative abundance of gut microbiota at the order level (a) and the phylum level (b). *P < 0.05, **P < 0.01. Error bars are SD (n= 3). (BMP 39361 KB)
11064_2018_2620_MOESM3_ESM.tif (225 kb)
Fig. S3 Relative abundance of Firmicutes (a) and Akkermansia (b). (TIF 225 KB)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Feng Lai
    • 1
  • Rong Jiang
    • 2
  • Wenjun Xie
    • 1
  • Xinrong Liu
    • 1
  • Yong Tang
    • 3
  • Hong Xiao
    • 1
  • Jieying Gao
    • 1
  • Yan Jia
    • 1
  • Qunhua Bai
    • 1
  1. 1.School of Public Health and ManagementChongqing Medical UniversityChongqingPeople’s Republic of China
  2. 2.School of Basic MedicineChongqing Medical UniversityChongqingPeople’s Republic of China
  3. 3.Chongqing Orthopedics Hospital of Traditional Chinese MedicineChongqingPeople’s Republic of China

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