Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson's disease
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Hou YF, Shan C, Zhuang SY, Zhuang QQ, Ghosh A, Zhu KC, Kong XK, Wang SM, Gong YL, Yang YY, Tao B, Sun LH, Zhao HY, Guo XZ, Wang WQ, Ning G, Gu YY, Li ST, Liu JM
Journal
Microbiome
Year
2021
Keywords:
Gut microbiota, Osteocalcin, Parkinson’s disease, Propionate
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota. RESULTS: The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice. CONCLUSIONS: Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
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
- 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
- Treatment outcome measurement Treatment outcome measurement,treatment outcome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- 6-hydroxydopamine (6-OHDA) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- 6-OHDA was injected into the right striatum to establish the Parkinson Disease mouse model. 6-OHDA is a hydroxylated analog of the natural dopamine neurotransmitter and used to destroy nigral dopaminergic neurons and deplete the striatum of DA neurotransmitter after the injection
- Group 0 sample size Number of subjects in the control (unexposed) group
- 12
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
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
- ANOVA
- 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
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Source: Figure 4D and Supplementary Table 5
Description: Different Relative Abundances of gut microbiota in 6-OHDA-induced vs Control
Abundance in Group 1: increased abundance in 6-hydroxydopamine (6-OHDA) group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Lachnospiraceae | ||
| unclassified Eubacteriales | ||
| unclassified Lachnospiraceae | ||
| unclassified Rickenellaceae |
Revision editor(s): MyleeeA
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Source: Figure 4D and Supplementary Table 5
Description: Different Relative Abundances of gut microbiota in 6-OHDA-induced vs Control
Abundance in Group 1: decreased abundance in 6-hydroxydopamine (6-OHDA) group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidota | ||
| Erysipelotrichaceae | ||
| Muribaculaceae | ||
| Rickenellaceae | ||
| unclassified Muribaculaceae |
Revision editor(s): MyleeeA
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- 6-OHDA + OCN (Osteocalcin) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- 6-OHDA was injected into the right striatum to establish the Parkinson Disease mouse model. 6-OHDA is a hydroxylated analog of the natural dopamine neurotransmitter and used to destroy nigral dopaminergic neurons and deplete the striatum of DA neurotransmitter after the injection.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 7
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Source: Figure 4D and Supplementary Table 5
Description: Different Relative Abundances of gut microbiota in 6-OHDA-induced vs 6-OHDA + OCN (Osteocalcin) group.
Abundance in Group 1: increased abundance in 6-hydroxydopamine (6-OHDA) group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Lachnospiraceae | ||
| unclassified Eubacteriales | ||
| unclassified Lachnospiraceae |
Revision editor(s): MyleeeA
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Source: Figure 4D and Supplementary Table 5
Description: Different Relative Abundances of gut microbiota in 6-OHDA-induced vs 6-OHDA + OCN (Osteocalcin) group.
Abundance in Group 1: decreased abundance in 6-hydroxydopamine (6-OHDA) group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidota | ||
| Erysipelotrichaceae | ||
| Muribaculaceae | ||
| Rickenellaceae | ||
| unclassified Burkholderiales | ||
| unclassified Rickenellaceae | ||
| unclassified Muribaculaceae |
Revision editor(s): MyleeeA
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