Dysbiosis of gut microbiota inhibits NMNAT2 to promote neurobehavioral deficits and oxidative stress response in the 6-OHDA-lesioned rat model of Parkinson's disease

Study information

Reviewed Marked as Reviewed by Svetlana up on 2024-7-1

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

37208728

DOI Digital object identifier for electronic documents.

10.1186/s12974-023-02782-1

URI

Authors

Yu J, Meng J, Qin Z, Yu Y, Liang Y, Wang Y, Min D

Journal

Journal of neuroinflammation

Year

2023

Keywords:

Dysbiosis of gut microbiota, Fecal microbiota transplantation, NMNAT2, Neurobehavioral symptoms, Oxidative stress response, Parkinson’s disease

BACKGROUND: New data are accumulating on gut microbial dysbiosis in Parkinson's disease (PD), while the specific mechanism remains uncharacterized. This study aims to investigate the potential role and pathophysiological mechanism of dysbiosis of gut microbiota in 6-hydroxydopamine (6-OHDA)-induced PD rat models. METHODS: The shotgun metagenome sequencing data of fecal samples from PD patients and healthy individuals were obtained from the Sequence Read Archive (SRA) database. The diversity, abundance, and functional composition of gut microbiota were further analyzed in these data. After the exploration of the functional pathway-related genes, KEGG and GEO databases were used to obtain PD-related microarray datasets for differential expression analysis. Finally, in vivo experiments were performed to confirm the roles of fecal microbiota transplantation (FMT) and upregulated NMNAT2 in neurobehavioral symptoms and oxidative stress response in 6-OHDA-lesioned rats. RESULTS: Significant differences were found in the diversity, abundance, and functional composition of gut microbiota between PD patients and healthy individuals. Dysbiosis of gut microbiota could regulate NAD+ anabolic pathway to affect the occurrence and development of PD. As a NAD+ anabolic pathway-related gene, NMNAT2 was poorly expressed in the brain tissues of PD patients. More importantly, FMT or overexpression of NMNAT2 alleviated neurobehavioral deficits and reduced oxidative stress in 6-OHDA-lesioned rats. CONCLUSIONS: Taken together, we demonstrated that dysbiosis of gut microbiota suppressed NMNAT2 expression, thus exacerbating neurobehavioral deficits and oxidative stress response in 6-OHDA-lesioned rats, which could be rescued by FMT or NMNAT2 restoration.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-1

Curated date: 2024/03/13

Curator: Barrakat

Revision editor(s): Barrakat

Subjects

Location of subjects: China

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

Group 1 name Corresponds to the case (exposed) group for case-control studies: Parkinson's Disease (PD)-patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Individuals with early-stage Parkinson's disease

Group 0 sample size Number of subjects in the control (unexposed) group: 28

Group 1 sample size Number of subjects in the case (exposed) group: 31

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: 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)?: No

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

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

Alpha Diversity

Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa: decreased

Signature 1

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Curator: Barrakat

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Source: Figure 2B

Description: Difference in gut microbiota composition between Parkinson's Disease (PD)-patients and healthy individuals

Abundance in Group 1: increased abundance in Parkinson's Disease (PD)-patients

NCBI	Quality Control	Links
Adlercreutzia
Adlercreutzia equolifaciens
Akkermansia
Akkermansia muciniphila
Alistipes shahii
Bacteroidales bacterium
Verrucomicrobiaceae
Verrucomicrobiia
Verrucomicrobiales
Verrucomicrobiota
unclassified Bacteroidales

Revision editor(s): Barrakat

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Source: Figure 2B

Description: Difference in gut microbiota composition between Parkinson's Disease (PD)-patients and healthy individuals

Abundance in Group 1: decreased abundance in Parkinson's Disease (PD)-patients

NCBI	Quality Control	Links
Acidaminococcaceae
Actinomycetales
Bacilli
Catenibacterium mitsuokai
Erysipelotrichaceae
Erysipelotrichales
Erysipelotrichia
Gammaproteobacteria
Holdemanella biformis
Lachnospiraceae
Lactobacillales
Leyella stercorea
Negativicutes
Paraprevotella
Phascolarctobacterium
Phascolarctobacterium succinatutens
Prevotella
Prevotellaceae
Segatella copri
Selenomonadales
Streptococcaceae
Streptococcus
Streptococcus thermophilus
Veillonella atypica
[Clostridium] leptum
unclassified Erysipelotrichaceae
unclassified Paraprevotella
Catenibacterium
unclassified Escherichia
Coprococcus sp. ART55_1
unclassified Veillonella atypicaunclassified Veillonella atypica
unclassified Streptococcus thermophilusunclassified Streptococcus thermophilus

Revision editor(s): Barrakat, Scholastica