Effects of Fecal Microbiota Transplantation on Intestinal Microbial Characteristics and Clinical Phenotypes in Patients with Parkinson's Disease

Summary

This exploratory study of six patients with Parkinson’s disease who underwent fecal microbiota transplantation observed temporal changes in gut microbial diversity, taxonomic composition, and predicted functional profiles, alongside improvements in motor and non-motor symptoms. These findings provide preliminary evidence supporting further investigation of microbiota-based interventions.

Abstract

Alterations in the gut microbiota have been associated with Parkinson’s disease (PD), but longitudinal microbial changes after fecal microbiota transplantation (FMT) and their clinical associations remain poorly understood. This single-center retrospective observational study included 6 patients with PD, stratified into high- and low-severity subgroups based on disease duration (>6 years vs ≤6 years). Thirty-six fecal samples were collected before FMT and monthly for five months afterward. Microbial diversity, community structure, taxonomic composition, and predicted functional profiles were assessed using 16S ribosomal RNA gene sequencing. Analyses included alpha and beta diversity, taxonomic abundance, linear discriminant analysis effect size, Tax4Fun2-based functional prediction, and Spearman rank correlations between microbial features and clinical indicators. Descriptive analyses indicated differences in microbial richness, diversity, community structure, and predicted functions between severity subgroups and across post-FMT time points. At baseline, the low-severity subgroup had greater microbial richness and diversity than the high-severity subgroup, with relatively higher abundances of taxa including Bifidobacterium and Lactobacillus. One month after FMT, richness and diversity increased from baseline in the high-severity subgroup, accompanied by changes in taxonomic composition. Both subgroups showed time-associated variation in microbial diversity and predicted Kyoto Encyclopedia of Genes and Genomes pathway enrichment after FMT. Predicted functions included carbohydrate and amino acid metabolism, secondary metabolite biosynthesis, membrane transport, and signal transduction. Several operational taxonomic units correlated with indicators of motor impairment, constipation, sleep quality, functional status, and neuropsychiatric symptoms. FMT was therefore associated with longitudinal changes in gut microbial diversity, composition, and predicted functions, and specific microbial features were associated with motor and non-motor indicators. Given the small retrospective cohort, these findings are preliminary and warrant confirmation in larger controlled studies. Future studies should determine whether these microbial alterations are reproducible, persist beyond five months, reflect donor engraftment, and correspond to measurable clinical improvement after transplantation in PD.

Introduction

Parkinson’s disease (PD) is a common progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, and postural instability¹. While its pathogenesis remains incompletely elucidated, multiple factors, including neuroinflammation, environmental exposures, and genetic susceptibility, have been implicated in disease onset and progression². Epidemiological evidence indicates that PD is among the most common neurological disorders in older adults and is associated with a substantial burden of disability, with prevalence increasing with age³. Current treatments, pa....

Protocol

The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of The Second Affiliated Hospital of Nanjing Medical University (approval number: 2021-KY-100-01). Written informed consent was obtained from all participants.

This single-center retrospective observational study was conducted at the Department of Neurology, The Second Affiliated Hospital of Nanjing Medical University. From January 2022 to December 2023, a total of 32 patients with primary PD who met the Diagnostic Criteria for Parkinson’s Disease (2020 edition) were included. Ultimately, six patients who met s....

Results

Patient selection and baseline characteristics

Six patients with PD were included in the final analysis, including three males and three females. The median age was 69.0 years (range, 61–75), and the median body mass index was 22.6 kg/m². The cohort included two rigidity-dominant, two tremor-dominant, and two mixed clinical phenotypes. Baseline clinical characteristics are shown in Table 1.

Clinical characteristics differ.......

Discussion

FMT is a microbiota-based intervention that transfers fecal microbiota from a healthy donor to the recipient’s gut to restore intestinal microbial balance¹⁴. Growing evidence suggests that the gut microbiota plays an important role in maintaining nervous system homeostasis¹⁵. Evidence from the bidirectional gut-brain axis indicates that the gut microbiota may influence central nervous system inflammation, neurotransmitter metabolism, and behavioral responses in PD

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
MiSeq System	Illumina, Inc.	SY-410-1003	Benchtop short-read sequencing platform used for 16S rRNA V3–V4 amplicon sequencing with 2 × 300 bp paired-end chemistry.
Metagenome@KIN	World Fusion Co., Ltd.	v2.2.1; https://www.w-fusion.com/metagenome	Commercial software used for 16S rRNA taxonomic assignment and microbial-community analysis.
Microbial Identification Database (bacterial)	TechnoSuruga Laboratory Co., Ltd.	DB-BA, database v10.0; https://www.tecsrg.co.jp/services/enki/	Bacterial 16S rDNA reference database used for microbial identification.
341F primer	BGI Genomics Co., Ltd.	Custom oligonucleotide; no catalogue number	Forward primer sequence: 5′-CCTACGGGNGGCWGCAG-3′.
805R primer	BGI Genomics Co., Ltd.	Custom oligonucleotide; no catalogue number	Reverse primer sequence: 5′-GACTACHVGGGTATCTAATCC-3′.
16S rRNA gene sequencing service	BGI Genomics Co., Ltd. (Wuhan, China)	https://www.bgi.com/us/sequencing-services/rna-sequencing-solutions/16s18s-its-sequencing/	Commercial sequencing provider; performed library preparation, sequencing and initial quality control.
Eppendorf Safe-Lock microcentrifuge tubes, Biopur, 1.5 mL	Eppendorf SE	'0030121589	Sterile polypropylene tubes used to aliquot fecal samples for storage at −80 °C.
LEfSe	Segata Lab/bioBakery	v1.1.2; https://github.com/SegataLab/lefse	Linear discriminant analysis effect size software used to identify differentially abundant taxa and predicted pathways.
Tax4Fun2	Tax4Fun2 development team	v1.1.5; https://github.com/fjossandon/Tax4Fun2	R package used to infer Kyoto Encyclopedia of Genes and Genomes functional profiles from 16S rRNA data.
microeco R package	Chi Liu and contributors	v1.15.0; https://cran.r-project.org/package=microeco	Community-ecology analysis and visualization package for microbial abundance and diversity analyses.
R software	R Foundation for Statistical Computing	Version not reported; https://www.r-project.org/	Statistical computing environment used for clinical and microbiome analyses; the exact version should be confirmed by the authors.
GenFMTer automated fecal microbiota purification system	Nanjing FMT Medical Co., Ltd.	Model: GenFMTer; https://en.fmtmed.com/	Automated system used for standardized centrifugation, washing and preparation of the fecal microbiota suspension.