Parasite-Derived Excretory-Secretory Products Alleviate Gut Microbiota Dysbiosis and Improve Cognitive Impairment Induced by a High-Fat Diet
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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
Wu J, Zhu Y, Zhou L, Lu Y, Feng T, Dai M, Liu J, Xu W, Cheng W, Sun F, Liu H, Pan W, Yang X
Journal
Frontiers in immunology
Year
2021
Keywords:
Echinococcus granulosus, cognition, excretory-secretory products, gut microbiota, microbiota-gut-brain axis, neuroinflammation, obesity
High-fat (HF) diet-induced neuroinflammation and cognitive decline in humans and animals have been associated with microbiota dysbiosis via the gut-brain axis. Our previous studies revealed that excretory-secretory products (ESPs) derived from the larval Echinococcus granulosus (E. granulosus) function as immunomodulators to reduce the inflammatory response, while the parasitic infection alleviates metabolic disorders in the host. However, whether ESPs can improve cognitive impairment under obese conditions remain unknown. This study aimed to investigate the effects of E. granulosus-derived ESPs on cognitive function and the microbiota-gut-brain axis in obese mice. We demonstrated that ESPs supplementation prevented HF diet-induced cognitive impairment, which was assessed behaviorally by nest building, object location, novel object recognition, temporal order memory, and Y-maze memory tests. In the hippocampus (HIP) and prefrontal cortex (PFC), ESPs suppressed neuroinflammation and HF diet-induced activation of the microglia and astrocytes. Moreover, ESPs supplementation improved the synaptic ultrastructural impairments and increased both pre- and postsynaptic protein levels in the HIP and PFC compared to the HF diet-treated group. In the colon, ESPs reversed the HF diet-induced gut barrier dysfunction, increased the thickness of colonic mucus, upregulated the expression of zonula occludens-1 (ZO-1), attenuated the translocation of bacterial endotoxins, and decreased the colon inflammation. Notably, ESPs supplementation alleviated the HF diet-induced microbiota dysbiosis. After clarifying the role of antibiotics in obese mice, we found that broad-spectrum antibiotic intervention abrogated the effects of ESPs on improving the gut microbiota dysbiosis and cognitive decline. Overall, the present study revealed for the first time that the parasite-derived ESPs alleviate gut microbiota dysbiosis and improve cognitive impairment induced by a high-fat diet. This finding suggests that parasite-derived molecules may be used to explore novel drug candidates against obesity-associated neurodegenerative diseases.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-2-5
Curated date: 2024/10/30
Curator:
Revision editor(s):
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
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low-Fat Diet (LF) group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High-Fat Diet (HF) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes mice receiving the High Fat diet (60% fat by weight) and intraperitoneally injected with 200 ml vehicle control twice a week in the Shannon Index.
- 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
- 12
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
- 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
- Matched on Factors on which subjects have been matched on in a case-control study
- body weight, Matched on: "fat mass" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.fat mass
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- body weight, diet, antibiotic, Confounders controlled for: "fat mass" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.fat mass
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Needs review
Curated date: 2024/11/04
Curator: Joiejoie
Revision editor(s): WikiWorks, MyleeeA, KateRasheed, Joiejoie
Source: Figure 5I
Description: Relative abundance of taxa in the LF vs HF groups
Abundance in Group 1: increased abundance in
Revision editor(s): WikiWorks, MyleeeA, KateRasheed, Joiejoie
Signature 2
Needs review
Curated date: 2024/11/04
Curator: Joiejoie
Revision editor(s): WikiWorks, MyleeeA, KateRasheed, Joiejoie
Source: Figure 5I
Description: Relative abundance of taxa between the LF and HF groups
Abundance in Group 1: decreased abundance in
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidales | ||
| Bacteroidia | ||
| Bacteroidota | ||
| Muribaculaceae | ||
| Parabacteroides | ||
| Parasutterella |
Revision editor(s): WikiWorks, MyleeeA, KateRasheed, Joiejoie
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-2-5
Curated date: 2024/11/13
Curator:
Revision editor(s):
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- High-Fat Diet with Excretory-secretory products (HFE) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes mice receiving the High Fat diet (60% fat by weight) and intraperitoneally injected with 200 ml vehicle control twice a week for the Shannon Index.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Needs review
Curated date: 2024/11/13
Curator: MyleeeA
Revision editor(s): WikiWorks, MyleeeA, KateRasheed, Joiejoie
Source: Figure 5J
Description: Relative abundance of taxa in the HF and HFE groups
Abundance in Group 1: increased abundance in
| NCBI | Quality Control | Links |
|---|---|---|
| Lactobacillus intestinalis | ||
| Odoribacter | ||
| Romboutsia | ||
| unclassified Eubacteriales |
Revision editor(s): WikiWorks, MyleeeA, KateRasheed, Joiejoie
Signature 2
Needs review
Curated date: 2024/11/13
Curator: MyleeeA
Revision editor(s): WikiWorks, MyleeeA, KateRasheed, Joiejoie
Source: Figure 5J
Description: Relative abundance of taxa between the HF and HFE groups
Abundance in Group 1: decreased abundance in
Revision editor(s): WikiWorks, MyleeeA, KateRasheed, Joiejoie
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-2-5
Curated date: 2024/12/27
Curator:
Revision editor(s):
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Low-Fat Diet (LF) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes mice receiving the High Fat diet (60% fat by weight) and intraperitoneally injected with 200 ml vehicle control twice a week in the Simpson Index.
Lab analysis
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- log transformation
- Statistical test
- ANOVA
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- decreased
Signature 1
Needs review
Source: Fig. 5E
Description: Relative abundance of taxa in the HF and LF groups using ANOVA
Abundance in Group 1: decreased abundance in
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidota |
Revision editor(s): KateRasheed, WikiWorks
Signature 2
Needs review
Source: Fig. 5D, 5G, 5K
Description: Relative abundance of taxa in the HF and LF groups using ANOVA
Abundance in Group 1: increased abundance in
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Deltaproteobacteria | ||
| Desulfovibrionaceae | ||
| Desulfovibrionales | ||
| Pseudomonadota |
Revision editor(s): KateRasheed, WikiWorks
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2025-2-5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- High-Fat Diet with Excretory-secretory products (HFE) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes mice receiving the High Fat diet (60% fat by weight) and intraperitoneally injected with 200 ml vehicle control twice a week for the Simpson Index.
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
Signature 1
Needs review
Source: Fig. 5L
Description: Relative abundance of taxa in the HF and HFE groups using ANOVA
Abundance in Group 1: increased abundance in High-Fat Diet (HF) group
| NCBI | Quality Control | Links |
|---|---|---|
| Odoribacter |
Revision editor(s): KateRasheed, WikiWorks
Signature 2
Needs review
Source: Fig. 5D, 5G, 5K
Description: Relative abundance of taxa in the HF and HFE groups using ANOVA
Abundance in Group 1: decreased abundance in High-Fat Diet (HF) group
| NCBI | Quality Control | Links |
|---|---|---|
| Bacillota | ||
| Pseudomonadota | ||
| Desulfovibrionaceae | ||
| Desulfovibrionales | ||
| Deltaproteobacteria |
Revision editor(s): KateRasheed, WikiWorks
Experiment 21
Reviewed Marked as Reviewed by Svetlana up on 2025-2-5
Curated date: 2025/02/02
Curator:
Revision editor(s):
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- High-Fat ESPs supplement with antibiotics (HFE+AB) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes the HFE group given a cocktail of antibiotics ( HFE+Ab) in the drinking water to investigate the role of gut microbiota in ESPs intervention.
- 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
Statistical Analysis
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