Implications of gut microbiota dysbiosis and metabolic changes in prion disease

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Reviewed Marked as Reviewed by Svetlana up on 2024-7-15
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Yang D, Zhao D, Shah SZA, Wu W, Lai M, Zhang X, Li J, Guan Z, Zhao H, Li W, Gao H, Zhou X, Yang L
Journal
Neurobiology of disease
Year
2020
Keywords:
Metabolomics, Microbiome, Multi-omics analysis, Prion infection, Short chain fatty acids
Evidence of the gut microbiota influencing neurodegenerative diseases has been reported for several neural diseases. However, there is little insight regarding the relationship between the gut microbiota and prion disease. Here, using fecal samples of 12 prion-infected mice and 25 healthy controls, we analyzed the structure of the gut microbiota and metabolic changes by 16S rRNA sequencing and LC-MS-based metabolomics respectively as multi-omic analyses. Additionally, SCFAs and common amino acids were detected by GC-MS and UPLC respectively. Enteric changes induced by prion disease affected both structure and abundances of the gut microbiota. The gut microbiota of infected mice displayed greater numbers of Proteobacteria and less Saccharibacteria at the phylum level and more Lactobacillaceae and Helicobacteraceae and less Prevotellaceae and Ruminococcaceae at the family level. A total of 145 fecal metabolites were found to be significantly different in prion infection, and most (114) of these were lipid metabolites. Using KEGG pathway enrichment analysis, we found that 3 phosphatidylcholine (PC) compounds significantly decreased and 4 hydrophobic bile acids significantly increased. Decreases of 8 types of short-chain acids (SCFAs) and increases of Cys and Tyr and decreases of His, Trp, and Arg were observed in prion infection. Correlation analysis indicated that the gut microbiota changes observed in our study may have been the shared outcome of prion disease. These findings suggest that prion disease can cause significant shifts in the gut microbiota. Certain bacterial taxa can then respond to the resulting change to the enteric environment by causing dramatic shifts in metabolite levels. Our data highlight the health impact of the gut microbiota and related metabolites in prion disease.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

Curated date: 2024/03/15

Curator: Ikehdarlington

Revision editor(s): Ikehdarlington, Scholastica

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
Prion disease prion disease,prion disease pathway,prion induced disorder,prion protein disease,spongiform encephalopathy,Prion disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy Control (C)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prion-infected mice (R)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Prion-infected mice
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
12

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)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased
Richness Number of species
decreased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

Curated date: 2024/03/18

Curator: Ikehdarlington

Revision editor(s): Ikehdarlington, Scholastica

Source: Fig. 2B

Description: Differentially abundant bacterial taxa in prion-infected groups versus healthy control groups.

Abundance in Group 1: increased abundance in Prion-infected mice (R)

NCBI Quality ControlLinks
Bacilli
Campylobacterales
Epsilonproteobacteria
Helicobacter
Helicobacteraceae
Lactobacillaceae
Lactobacillales
Lactobacillus
Pseudomonadota

Revision editor(s): Ikehdarlington, Scholastica

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-7-15

Curated date: 2024/03/18

Curator: Ikehdarlington

Revision editor(s): Ikehdarlington, Scholastica

Source: Fig. 2B

Description: Differentially abundant bacterial taxa in prion-infected groups versus healthy control groups.

Abundance in Group 1: decreased abundance in Prion-infected mice (R)

NCBI Quality ControlLinks
Alloprevotella
Candidatus Saccharibacteria
Candidatus Saccharimonas
Oscillospiraceae
uncultured Oscillospiraceae bacterium
Prevotellaceae
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group

Revision editor(s): Ikehdarlington, Scholastica