Fibroblast growth factor 21 ameliorates behavior deficits in Parkinson's disease mouse model via modulating gut microbiota and metabolic homeostasis

Study information

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Reviewed Marked as Reviewed by Svetlana up on 2024-6-27

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

37334756

DOI Digital object identifier for electronic documents.

https://doi.org/10.1111/cns.14302

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651963/

Authors

Yang C, Wang W, Deng P, Wang X, Zhu L, Zhao L, Li C, Gao H

Journal

CNS neuroscience & therapeutics

Year

2023

Keywords:

FGF21, Parkinson's disease, metabolism, microbiota-gut-brain metabolic axis, neurotransmitter

AIMS: The effects of FGF21 on Parkinson's disease (PD) and its relationship with gut microbiota have not been elucidated. This study aimed to investigate whether FGF21 would attenuate behavioral impairment through microbiota-gut-brain metabolic axis in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mice model. METHODS: Male C57BL/6 mice were rendomized into 3 groups: vehicle (CON); MPTP 30 mg/kg/day i.p. injection (MPTP); FGF21 1.5 mg/kg/d i.p. injection plus MPTP 30 mg/kg/day i.p. injection (FGF21 + MPTP). The behavioral features, metabolimics profiling, and 16 s rRNA sequencing were performed after FGF21 treatment for 7 days. RESULTS: MPTP-induced PD mice showed motor and cognitive deficits accompanied by gut microbiota dysbiosis and brain-region-specific metabolic abnormalities. FGF21 treatment dramatically attenuated motor and cognitive dysfunction in PD mice. FGF21 produced a region-specific alteration in the metabolic profile in the brain in ways indicative of greater ability in neurotransmitter metabolism and choline production. In addition, FGF21 also re-structured the gut microbiota profile and increased the relative abundance of Clostridiales, Ruminococcaceae, and Lachnospiraceae, thereby rescuing the PD-induced metabolic disorders in the colon. CONCLUSION: These findings indicate that FGF21 could affect behavior and brain metabolic homeostasis in ways that promote a favorable colonic microbiota composition and through effects on the microbiota-gut-brain metabolic axis.

Experiment 1

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Subjects

Location of subjects

China

Host species Species from which microbiome was sampled. Contact us to have more species added.

Mus musculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology

Colon Hindgut,Large bowel,Posterior intestine,Colon,colon

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Group 0 name Corresponds to the control (unexposed) group for case-control studies

Control (CON groups)

Group 1 name Corresponds to the case (exposed) group for case-control studies

MPTP (untreated PD mice)

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) induced Parkinson's disease (PD) mice model.

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

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Ion Torrent

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

4

Alpha Diversity

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

unchanged

Richness Number of species

decreased

Signature 1

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Curated date: 2024/03/13

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, WikiWorks

Source: Figure 5A, Text

Description: LEfSe analysis with LDA score representing statistical bacterial differences in colonic microbiota between the PD (positive score) and CON groups (negative score).

Abundance in Group 1: increased abundance in

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Muribaculaceae
Bacteroidaceae
Bacteroides
Prevotellaceae
Alloprevotella
Tannerellaceae
Parabacteroides

Revision editor(s): Fiddyhamma, WikiWorks

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Source: Figure 5A, Text

Description: LEfSe analysis with LDA score representing statistical bacterial differences in colonic microbiota between the PD (positive score) and CON groups (negative score).

Abundance in Group 1: decreased abundance in

NCBI	Quality Control	Links
Candidatus Saccharimonas
Clostridia
Eubacteriales
Helicobacter mastomyrinus
Lachnospiraceae
Marinifilaceae
Mollicutes
Mycoplasmatota
Odoribacter
Oscillospiraceae
bacterium
unclassified Oscillospiraceae
Ureaplasma

Revision editor(s): Fiddyhamma, WikiWorks

Experiment 2

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Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Clinical treatment Clinical treatment,clinical treatment

Group 0 name Corresponds to the control (unexposed) group for case-control studies

FGF21 + MPTP mice (mice treated with Fibroblast growth factor 21 (FGF21))

Lab analysis

Statistical Analysis

Alpha Diversity

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

unchanged

Richness Number of species

unchanged

Signature 1

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Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, WikiWorks

Source: Figure 5C, Text

Description: LEfSe analysis with LDA score representing statistical bacterial differences in colonic microbiota between the PD (positive score) and FGF21 groups (negative score).

Abundance in Group 1: increased abundance in

NCBI	Quality Control	Links
Bacillales
Mammaliicoccus lentus
Staphylococcaceae
Staphylococcus

Revision editor(s): Fiddyhamma, WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Svetlana up on 2024-6-27

Curated date: 2024/03/13

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma, WikiWorks

Source: Figure 5C, Text

Description: LEfSe analysis with LDA score representing statistical bacterial differences in colonic microbiota between the PD (positive score) and FGF21 groups (negative score).

Abundance in Group 1: decreased abundance in

NCBI	Quality Control	Links
Candidatus Saccharimonas
Clostridia
Deltaproteobacteria
Desulfovibrionaceae
Desulfovibrionales
Eubacteriales
Lachnospiraceae
Oscillospiraceae
Ruminiclostridium papyrosolvens
bacterium
unclassified Oscillospiraceae

Revision editor(s): Fiddyhamma, WikiWorks