A prebiotic dietary pilot intervention restores faecal metabolites and may be neuroprotective in Parkinson's Disease

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-23
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Bedarf JR, Romano S, Heinzmann SS, Duncan A, Traka MH, Ng D, Segovia-Lizano D, Simon MC, Narbad A, Wüllner U, Hildebrand F
Journal
NPJ Parkinson's disease
Year
2025
Current treatment of Parkinson's Disease (PD) remains symptomatic, and disease-modifying approaches are urgently required. A promising approach is to modify intestinal microbiota and key metabolites of bacterial fermentation: short-chain fatty acids (SCFA), which are decreased in PD. A prospective, controlled pilot study (DRKS00034528) was conducted on 11 couples (PD patient plus healthy spouse as control (CO)). Participants followed a 4-week diet rich in dietary fibre, including intake of the prebiotic Lactulose. Gut metagenomes, faecal and urinary metabolites, and clinical characteristics were assessed. The dietary intervention significantly augmented faecal SCFA and increased Bifidobacteria spp., reducing PD-related gastrointestinal symptoms. The pre-existing bacterial dysbiosis in PD (depletion of Blautia, Dorea, Erysipelatoclostridium) persisted. Bacterial metabolite composition in faeces and urine positively changed with the intervention: Brain-relevant gut metabolic functions involved in neuroprotective and antioxidant pathways, including S-adenosyl methionine, glutathione, and inositol, improved in PD. These promising results warrant further investigation in larger cohorts.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/09

Curator: Shulamite

Revision editor(s): Shulamite, KateRasheed

Subjects

Location of subjects
Germany
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to diet Response to diet,response to diet
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy spouses after prebiotics (CO group)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Parkinson's Disease patients after prebiotics (PD group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patient diagnosed with parkinson disease after prebiotics.
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
10
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 Months

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Matched on Factors on which subjects have been matched on in a case-control study
age

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
increased
Richness Number of species
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/10

Curator: Shulamite

Revision editor(s): Shulamite

Source: Fig 2E

Description: Several genera were markedly reduced in the PD group after prebiotics, paralleled by several trends

Abundance in Group 1: increased abundance in Parkinson's Disease patients after prebiotics (PD group)

NCBI Quality ControlLinks
Christensenellales

Revision editor(s): Shulamite

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/10

Curator: Shulamite

Revision editor(s): Shulamite, KateRasheed

Source: Fig 2E

Description: Several genera were markedly reduced in the PD group after prebiotics, paralleled by several trends

Abundance in Group 1: decreased abundance in Parkinson's Disease patients after prebiotics (PD group)

NCBI Quality ControlLinks
Blautia ABlautia A
Dorea
Thomasclavelia
Anaerovoracaceae
Eubacterium IEubacterium I

Revision editor(s): Shulamite, KateRasheed

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/13

Curator: Shulamite

Revision editor(s): Shulamite, KateRasheed

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Health spouse (CO )before prebiotics
Group 1 name Corresponds to the case (exposed) group for case-control studies
Healthy spouse (CO) after prebiotics
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Healthy spouses who do not have Parkinson's disease

Lab analysis

Statistical Analysis

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/10

Curator: Shulamite

Revision editor(s): Shulamite, KateRasheed

Source: Supplementary Fig 3C

Description: Before vs after comparisons (Wilcoxon signed-rank test revealed that several Bifidobacteria spp. increased after prebiotics boxplots show a relative abundance of taxa. n=4 were also enriched in CO individuals.

Abundance in Group 1: increased abundance in Healthy spouse (CO) after prebiotics

NCBI Quality ControlLinks
Bifidobacterium adolescentis
Bifidobacterium breve
Bifidobacterium longum
Bifidobacterium pseudocatenulatum

Revision editor(s): Shulamite, KateRasheed

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/10

Curator: Shulamite

Revision editor(s): Shulamite, KateRasheed

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Parkinson's disease IDIOPATHIC PARKINSON DIS,Idiopathic Parkinson Disease,Idiopathic Parkinson's Disease,IDIOPATHIC PARKINSONS DIS,Idiopathic PD,LEWY BODY PARKINSON DIS,Lewy Body Parkinson Disease,Lewy Body Parkinson's Disease,Paralysis agitans,paralysis agitans,PARKINSON DIS,PARKINSON DIS IDIOPATHIC,Parkinson disease,Parkinson Disease, Idiopathic,Parkinson syndrome,Parkinson's,Parkinson's disease,Parkinson's disease (disorder),Parkinson's disease NOS,Parkinson's disease NOS (disorder),Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinson's syndrome,Parkinsonian disorder,Parkinsonism, Primary,Parkinsons,PARKINSONS DIS,PARKINSONS DIS IDIOPATHIC,PARKINSONS DIS LEWY BODY,Parkinsons disease,Primary Parkinsonism,parkinson's disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
PD before prebiotics
Group 1 name Corresponds to the case (exposed) group for case-control studies
PD after prebiotics
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Parkinson's disease patient after prebiotics.

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/10

Curator: Shulamite

Revision editor(s): Shulamite

Source: Supplementary Fig. 3c

Description: Before-vs.-after comparisons (Wilcoxon signed-rank test) revealed that several Bifidobacteria spp. increased after prebiotics. Boxplots show a relative abundance of taxa. n=6 Bifidobacteria spp. were the only sign. different in PD (Strept. Thermophilus, UMGS1975).

Abundance in Group 1: increased abundance in PD after prebiotics

NCBI Quality ControlLinks
Bifidobacterium adolescentis
Bifidobacterium angulatum
Bifidobacterium breve
Bifidobacterium longum
Bifidobacterium pseudocatenulatum
Bifidobacterium ruminantium
Christensenellales

Revision editor(s): Shulamite

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/10

Curator: Shulamite

Revision editor(s): Shulamite

Source: Supplementary Fig. 3c

Description: Before-vs.-after comparisons (Wilcoxon signed-rank test) revealed that several Bifidobacteria spp. increased after prebiotics. Boxplots show a relative abundance of taxa. n=6 Bifidobacteria spp. were the only sign. different in PD (Strept. Thermophilus, UMGS1975).

Abundance in Group 1: decreased abundance in PD after prebiotics

NCBI Quality ControlLinks
Streptococcus thermophilus

Revision editor(s): Shulamite

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/22

Curator: Shulamite

Revision editor(s): Shulamite, KateRasheed

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to diet Response to diet,response to diet
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Health spouse (CO )before prebiotics
Group 1 name Corresponds to the case (exposed) group for case-control studies
Parkinson's Disease before prebiotics
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients diagnosed with Parkinson's disease before prebiotics.
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 Months.

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
age

Alpha Diversity

Pielou Quantifies how equal the community is numerically
unchanged
Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-23

Curated date: 2025/04/22

Curator: Shulamite

Revision editor(s): Shulamite

Source: Fig 2E

Description: Several genera were markedly reduced in the PD group before prebiotics, paralleled by several trends

Abundance in Group 1: decreased abundance in Parkinson's Disease before prebiotics

NCBI Quality ControlLinks
Blautia ABlautia A

Revision editor(s): Shulamite