Cited by 147Parkinson's Disease Mechanisms and TreatmentsGut microbiota and healthGastrointestinal motility and disorders

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Efficacy of fecal microbiota transplantation in patients with Parkinson’s disease: clinical trial results from a randomized, placebo-controlled design

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Abstract

The occurrence and development of Parkinson’s disease (PD) have been demonstrated to be related to gut dysbiosis, however, the impact of fecal microbiota transplantation (FMT) on microbiota engraftment in PD patients is uncertain. We performed a randomized, placebo-controlled trial at the Department of Neurology, Army Medical University Southwest Hospital in China (ChiCTR1900021405) from February 2019 to December 2019. Fifty-six participants with mild to moderate PD (Hoehn-Yahr stage 1–3) were randomly assigned to the FMT and placebo group, 27 patients in the FMT group and 27 in the placebo group completed the whole trial. During the follow-up, no severe adverse effect was observed, and patients with FMT treatment showed significant improvement in PD-related autonomic symptoms compared with the placebo group at the end of this trial (MDS-UPDRS total score, group×time effect, B = -6.56 [−12.98, −0.13], P < 0.05). Additionally, FMT improved gastrointestinal disorders and a marked increase in the complexity of the microecological system in patients. This study demonstrated that FMT through oral administration is clinically feasible and has the potential to improve the effectiveness of current medications in the clinical symptoms of PD patients.

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Crossref · 10.1080/19490976.2023.2284247

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Figures

Figure 1. Flow chart of patients included and excluded in this trial.
Figure 1. Flow chart of patients included and excluded in this trial.CC BY · PubMed Central
Figure 2. The baseline characteristics of gut microbiota in donors and patients with PD (placebo/FMT group). a-b: α diversity of gut microbiota in different groups according to estimate of Faith_Pd (a) and estimate of Observed_Otus (b) (ns, not significant, ***p <.001; Wilcoxon sum-rank test.); c: Principal coordinate analysis (PCoA) of the microbiota between three groups by R package vegan. (ANOSIM; donor vs. F.0W, R = 0.2055, p = .125; donor vs. P.0W, R = 0.1797, p = .15; F.0W vs. P.0W, R = 0.0041, p = .338); D: bar plots showing the relative abundance of gut microbiota of three groups of individuals at the phylum level, with different colors corresponding to different phyla; E: heat map showing the relative abundance of three groups of individuals at the genus level (samples from the same donor was marked as D1, D2, D3, and D4). Only significantly different genera were shown between donors and patients with PD (R package ALDEx2, we.Ep <.05 and wi.Ep <.05).
Figure 2. The baseline characteristics of gut microbiota in donors and patients with PD (placebo/FMT group). a-b: α diversity of gut microbiota in different groups according to estimate of Faith_Pd (a) and estimate of Observed_Otus (b) (ns, not significant, ***p <.001; Wilcoxon sum-rank test.); c: Principal coordinate analysis (PCoA) of the microbiota between three groups by R package vegan. (ANOSIM; donor vs. F.0W, R = 0.2055, p = .125; donor vs. P.0W, R = 0.1797, p = .15; F.0W vs. P.0W, R = 0.0041, p = .338); D: bar plots showing the relative abundance of gut microbiota of three groups of individuals at the phylum level, with different colors corresponding to different phyla; E: heat map showing the relative abundance of three groups of individuals at the genus level (samples from the same donor was marked as D1, D2, D3, and D4). Only significantly different genera were shown between donors and patients with PD (R package ALDEx2, we.Ep <.05 and wi.Ep <.05).CC BY · PubMed Central
Figure 3. Comparison of gut microbiota between responders and non-responders after FMT treatment. A: patients who underwent FMT treatment had different responses during follow-up according to the MDS-UPDRS score, and the FMT cohort was subdivided into FMT responders (FMT.R, red lines) and FMT non-responders (FMT.NR, cyan lines) based on MDS-UPDRS 2, FMT.R showed a remarkable decrease in MDS-UPDRS total, part 2, part 3, and part 4 score (*: P < .05, **: P < .01, ***: P < .001, ***: P < .0001, generalized estimating equation); B: schematic illustration of subgroup analysis in the FMT arm; C: α-diversity of gut microbiota in FMT.NR and FMT.R subgroups according to estimate of richness; D: Principal coordinates analysis (PCoA) of the microbiota based on the unweighted unifrac distance between FMT.R and FMT.NR subgroups at the end of this trial by R package Vegan; E: metagenomic sequencing analysis showed there are 20 microbial species with significantly different abundance by comparing FMT.NR with FMT.R subgroup; F: the correlation analysis of gut microbiota taxa and clinic outcome of gastrointestinal disorders, PD symptoms, cognition, and depression (*p <.05, **P <.01, Spearman correlation analysis); G: different functional pathways between FMT.NR and FMT.R subgroup; H: the correlation analysis of gut microbiota functional pathways and clinic outcomes. (*p <.05, **P <.01, Spearman correlation analysis).
Figure 3. Comparison of gut microbiota between responders and non-responders after FMT treatment. A: patients who underwent FMT treatment had different responses during follow-up according to the MDS-UPDRS score, and the FMT cohort was subdivided into FMT responders (FMT.R, red lines) and FMT non-responders (FMT.NR, cyan lines) based on MDS-UPDRS 2, FMT.R showed a remarkable decrease in MDS-UPDRS total, part 2, part 3, and part 4 score (*: P < .05, **: P < .01, ***: P < .001, ***: P < .0001, generalized estimating equation); B: schematic illustration of subgroup analysis in the FMT arm; C: α-diversity of gut microbiota in FMT.NR and FMT.R subgroups according to estimate of richness; D: Principal coordinates analysis (PCoA) of the microbiota based on the unweighted unifrac distance between FMT.R and FMT.NR subgroups at the end of this trial by R package Vegan; E: metagenomic sequencing analysis showed there are 20 microbial species with significantly different abundance by comparing FMT.NR with FMT.R subgroup; F: the correlation analysis of gut microbiota taxa and clinic outcome of gastrointestinal disorders, PD symptoms, cognition, and depression (*p <.05, **P <.01, Spearman correlation analysis); G: different functional pathways between FMT.NR and FMT.R subgroup; H: the correlation analysis of gut microbiota functional pathways and clinic outcomes. (*p <.05, **P <.01, Spearman correlation analysis).CC BY · PubMed Central
Figure 4. The microbial network analysis in participants after FMT. a: visualization of constructed MENs in FMT.R and FMT.NR subgroups at different times. 18 large modules are shown in different colors, and smaller modules are shown in gray. b-e: comparison of the genera co-occurrence networks between different subgroups. Network plots describing the co-occurrence of bacterial genera in the gut microbiota of donor (b), F.0W (c), F.12W.NR (d), F.12W.R (e) based on the Spearman correlation algorithms (r ≥ 0.7, p < .05), bacterial genera with at least 0.01% of relative abundance in at least 20% of the samples in each group were plotted. Each node presents a bacterial genus. The node size indicates the relative abundance of each genus per group, and the density of the dashed line represents the Spearman coefficient. Red links stand for positive interactions between nodes, and green links stand for negative interactions; f: discrepancies of the genera co-occurrence networks among groups based on the 16S rRNA data. The centralities (rank of the closeness) and discrepancies of nodes in four subgroups’ co-occurrence networks were counted, respectively.
Figure 4. The microbial network analysis in participants after FMT. a: visualization of constructed MENs in FMT.R and FMT.NR subgroups at different times. 18 large modules are shown in different colors, and smaller modules are shown in gray. b-e: comparison of the genera co-occurrence networks between different subgroups. Network plots describing the co-occurrence of bacterial genera in the gut microbiota of donor (b), F.0W (c), F.12W.NR (d), F.12W.R (e) based on the Spearman correlation algorithms (r ≥ 0.7, p < .05), bacterial genera with at least 0.01% of relative abundance in at least 20% of the samples in each group were plotted. Each node presents a bacterial genus. The node size indicates the relative abundance of each genus per group, and the density of the dashed line represents the Spearman coefficient. Red links stand for positive interactions between nodes, and green links stand for negative interactions; f: discrepancies of the genera co-occurrence networks among groups based on the 16S rRNA data. The centralities (rank of the closeness) and discrepancies of nodes in four subgroups’ co-occurrence networks were counted, respectively.CC BY · PubMed Central

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Metadata

Authors
Cheng, Y., Tan, G., Zhu, Q., Wang, C., Ruan, G., Ying, S., Qie, J., Hu, X., Xiao, Z., Xu, F., Chen, L., Chen, M., Pei, Y., Zhang, H., Tian, Y., Chen, D., Liu, X., Huang, H., & Wei, Y.
Affiliations
  • Army Medical University (CN)
  • Suzhou Municipal Hospital (CN)
  • Department of Pathogen Biology-Microbiology Division, Key Laboratory of Pathogen of Jiangsu Province; The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital Gusu School, Nanjing Medical University, Jiangsu, China
Corresponding author
  • Liu, Xingyin
  • Huang, Heqing
  • Wei, Yanling
Venue
Gut Microbes
Published
2023-12-06
Volume
15
Issue
2
Pages
2284247-2284247
ISSN
  • 1949-0976 (ISSN-L)
  • 1949-0984
OpenAlex
W4389451466
Cited by
147
References
53
Citations by year
2026: 42 · 2025: 73 · 2024: 32
FWCI
25.01
Type
journal article
Language
en
Open access
Locations
  • Gut Microbes (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • the National Natural Science Foundation of China (82172288)
  • the Special Project for Enhancement of Science and Technology Innovation Capability of Army Medical University (2019XLC3040)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
fecal microbiota transplantation, Parkinson's disease, gut dysbiosis, autonomic symptoms, gastrointestinal diseases, MDS-UPDRS, oral administration, treatment feasibility
MeSH terms
Gastrointestinal Microbiome, Fecal Microbiota Transplantation, China, Feces, Humans, Parkinson Disease, Treatment Outcome, Dysbiosis

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