Effects of the Lipid Metabolites and the Gut Microbiota in ApoE-/- Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis

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Reviewed Marked as Reviewed by KateRasheed on 2025-5-10
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Hu K, Liao XX, Wu XY, Wang R, Hu ZW, Liu SY, He WF, Zhou JJ
Journal
Frontiers in molecular biosciences
Year
2022
Keywords:
ApoE−/−, atherosclerosis, depression, gut microbiota, lipid metabolites, microbiota-gut-brain axis
Background: The diagnosis, treatment, and prevention of atherosclerosis co-depression are poor, so it is urgent to explore new targets. Based on the "microbiota-gut-brain axis," this study aimed to investigate the changes of lipid metabolites in the prefrontal cortex and hippocampus regions and the characteristics of the gut microbiota in ApoE-/- mice with atherosclerosis co-depression. Methods: ApoE-/- mice (hyperlipid feeding combined with binding, HFB group, n = 14, male) fed a high-fat diet for 16 weeks with binding stimulation were used as an animal model for atherosclerosis co-depression. The depression degree of mice was evaluated by body weight, sucrose preference test, open field test, and tail suspension test. Oil-red O staining, HE staining, and biochemical parameters were used to evaluate the damage degree of atherosclerosis in mice. LC-MS/MS technique for non-targeted lipidomics analysis was used to analyze the differential lipid metabolites in the prefrontal cortex and hippocampus regions of mice. 16S rDNA amplification sequencing was used to screen the differential gut microbial, and association analysis was performed with the differential lipid metabolites. Results: Compared with the normal control group (NC group), the HFB group showed depression-like behaviors and atherosclerosis-related pathological indicators. The differential lipid metabolites in the prefrontal cortex and hippocampus regions were mainly LPC, LPE, LPS, PC, PE, PS, PI, and GD1a, and were mainly enriched in the glycerophospholipid metabolism pathway and the retrograde endocannabinoid signaling pathway. At the same time, there were significant differences in the structure of the gut microbial community between the two groups. The abundance of Deferribacteres and Proteobacteria in the HFB group increased, while the abundance of Verrucomicrobia and Actinobacteria decreased at the phylum level; the abundance of Desulfovibrio, Clostridium_IV, Helicobacter and Pseudoflavonifractor increased, while the abundance of Akkermansia decreased at the genus level. Conclusion: Atherosclerosis co-depression of ApoE-/- mice of the prefrontal cortex and hippocampus lipid metabolism pathways of disorder and the changes of to the gut microbiota, which leads to abnormal white matter and synaptic dysfunction, increased gut inflammation, and decreased gut permeability, leading to the release of inflammatory cytokines, there is a strong correlation between both, it further confirmed the existence of the "microbiota-gut-brain axis."

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-5-10

Curated date: 2025/04/26

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp

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
Response to diet Response to diet,response to diet
Group 0 name Corresponds to the control (unexposed) group for case-control studies
NC (Normal Control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
HFB (Hyperlipid feeding combined with binding)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
ApoE−/− male mice fed a high-fat diet for 16 weeks with 1hour/day restraint (“binding”) to induce both atherosclerosis and depression‐like behavior
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
6

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)?
No

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-5-10

Curated date: 2025/04/29

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp

Source: Figure 5D & F

Description: Statistical plots showing differential taxa at phylum and genus levels between NC and HFB groups

Abundance in Group 1: increased abundance in HFB (Hyperlipid feeding combined with binding)

NCBI Quality ControlLinks
Desulfovibrio
Helicobacter
Pseudoflavonifractor
Pseudomonadota
Clostridium IVClostridium IV
Deferribacterota

Revision editor(s): Amaanarif, Anne-mariesharp

Signature 3

Reviewed Marked as Reviewed by KateRasheed on 2025-5-10

Curated date: 2025/04/29

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp

Source: Figures 5D & 5F

Description: Statistical plots showing differential taxa at phylum and genus levels between NC and HFB groups

Abundance in Group 1: decreased abundance in HFB (Hyperlipid feeding combined with binding)

NCBI Quality ControlLinks
Actinomycetota
Akkermansia
Verrucomicrobiota

Revision editor(s): Amaanarif, Anne-mariesharp

Experiment 2


Reviewed Marked as Reviewed by KateRasheed on 2025-5-10

Curated date: 2025/04/28

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Statistical test
LEfSe
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
Richness Number of species
unchanged

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-5-10

Curated date: 2025/05/04

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp

Source: Figure 5G, H

Description: LEfSe analyses showing differential microbial taxa in NC and HFB groups

Abundance in Group 1: increased abundance in HFB (Hyperlipid feeding combined with binding)

NCBI Quality ControlLinks
Acetatifactor
Aerococcaceae
Aerococcus
Anaerotruncus
Bacillales
Campylobacterales
Deferribacteraceae
Deferribacterales
Deferribacterota
Deltaproteobacteria
Desulfovibrio
Desulfovibrionaceae
Desulfovibrionales
Epsilonproteobacteria
Helicobacter
Helicobacteraceae
Mucispirillum
Oscillibacter
Oscillospiraceae
Paraprevotella
Pseudoflavonifractor
Pseudomonadota
Staphylococcaceae
Staphylococcus
Clostridium IVClostridium IV
Clostridium XIVbClostridium XIVb
Deferribacteres

Revision editor(s): Amaanarif, Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-5-10

Curated date: 2025/05/04

Curator: Amaanarif

Revision editor(s): Amaanarif, Anne-mariesharp

Source: Figure 5G, H

Description: LEfSe analyses showing differential microbial taxa in NC and HFB groups

Abundance in Group 1: decreased abundance in HFB (Hyperlipid feeding combined with binding)

NCBI Quality ControlLinks
Akkermansia
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Gemmiger
Parvibacter
Ruminococcus
Verrucomicrobiaceae
Verrucomicrobiales
Verrucomicrobiia
Verrucomicrobiota

Revision editor(s): Amaanarif, Anne-mariesharp