Gut Microbiota and Metabolome Alterations Associated with Parkinson's Disease

Study information

Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-30

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

32934117

DOI Digital object identifier for electronic documents.

10.1128/mSystems.00561-20

URI

https://pubmed.ncbi.nlm.nih.gov/32934117

Authors

Vascellari S, Palmas V, Melis M, Pisanu S, Cusano R, Uva P, Perra D, Madau V, Sarchioto M, Oppo V, Simola N, Morelli M, Santoru ML, Atzori L, Melis M, Cossu G, Manzin A

Journal

mSystems

Year

2020

Keywords:

16S RNA, PD, gut microbiota, metabolome

Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates of misfolded alpha-synuclein along the cerebral axis. Several studies report the association between intestinal dysbiosis and Parkinson's disease, although a cause-effect relationship remains to be established. Herein, the gut microbiota composition of 64 Italian patients with Parkinson's disease and 51 controls was determined using a next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry was also investigated. The most significant changes within the Parkinson's disease group highlighted a reduction in bacterial taxa, which are linked to anti-inflammatory/neuroprotective effects, particularly in the Lachnospiraceae family and key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, and Blautia The direct evaluation of fecal metabolites revealed changes in several classes of metabolites. Changes were seen in lipids (linoleic acid, oleic acid, succinic acid, and sebacic acid), vitamins (pantothenic acid and nicotinic acid), amino acids (isoleucine, leucine, phenylalanine, glutamic acid, and pyroglutamic acid) and other organic compounds (cadaverine, ethanolamine, and hydroxy propionic acid). Most modified metabolites strongly correlated with the abundance of members belonging to the Lachnospiraceae family, suggesting that these gut bacteria correlate with altered metabolism rates in Parkinson's disease.IMPORTANCE To our knowledge, this is one of the few studies thus far that correlates the composition of the gut microbiota with the direct analysis of fecal metabolites in patients with Parkinson's disease. Overall, our data highlight microbiota modifications correlated with numerous fecal metabolites. This suggests that Parkinson's disease is associated with gut dysregulation that involves a synergistic relationship between gut microbes and several bacterial metabolites favoring altered homeostasis. Interestingly, a reduction of short-chain fatty acid (SCFA)-producing bacteria influenced the shape of the metabolomics profile, affecting several metabolites with potential protective effects in the Parkinson group. On the other hand, the extensive impact that intestinal dysbiosis has at the level of numerous metabolic pathways could encourage the identification of specific biomarkers for the diagnosis and treatment of Parkinson's disease, also in light of the effect that specific drugs have on the composition of the intestinal microbiota.

Experiment 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-30

Curated date: 2023/04/02

Curator: Atrayees

Revision editor(s): Atrayees, Jacquelynshevin, Claregrieve1

Subjects

Location of subjects: Italy

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: 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: Healthy control

Group 1 name Corresponds to the case (exposed) group for case-control studies: Patients with Parkinson's disease

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients who have Parkinson's disease

Group 0 sample size Number of subjects in the control (unexposed) group: 51

Group 1 sample size Number of subjects in the case (exposed) group: 64

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: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

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: LEfSe

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

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Chao1 Abundance-based estimator of species richness: unchanged

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Richness Number of species: unchanged

Signature 1

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-30

Curated date: 2023/04/02

Curator: Atrayees

Revision editor(s): Atrayees

Source: Fig 2a

Description: significantly differential taxa between patients with Parkinson's disease and Healthy controls.

Abundance in Group 1: increased abundance in Patients with Parkinson's disease

NCBI	Quality Control	Links
Verrucomicrobiia
Verrucomicrobiaceae
Akkermansia
Pseudomonadota
Escherichia
Actinomycetota
Bifidobacterium
Bifidobacteriaceae
Veillonella
Streptococcaceae
Streptococcus
Clostridium
Serratia
Desulfonauticus
Desulfohalobiaceae
Microbacteriaceae
Coriobacteriaceae
Enterobacter
Slackia
Prosthecobacter
Eubacteriaceae
Acetobacterium
Anaerostipes
Desulfovibrio
Caldicellulosiruptor
Rickenellaceae

Revision editor(s): Atrayees

Signature 2

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Reviewed Marked as Reviewed by Claregrieve1 on 2023-5-30

Curated date: 2023/04/02

Curator: Atrayees

Revision editor(s): Atrayees

Source: Fig 2b

Description: significantly differential taxa between patients with Parkinson's disease and Healthy controls.

Abundance in Group 1: decreased abundance in Patients with Parkinson's disease

NCBI	Quality Control	Links
Comamonadaceae
Brevibacteriaceae
Butyrivibrio
Brevibacterium
Odoribacter
Pseudobutyrivibrio
Cyanobacteriota
Parabacteroides
Coprococcus
Dolichospermum
Sphingobacteriaceae
Sutterella
Alcaligenaceae
Lachnospira
Roseburia
Klebsiella
Candidatus Blochmanniella
Blautia
Lachnospiraceae
Bacteroides
Bacteroidaceae
Bacteroidia