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
Needs review
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
- Cognitive impairment Abnormality of cognition,Cognitive abnormality,Cognitive defects,Cognitive deficits,Cognitive impairment,Intellectual impairment,cognitive impairment
- 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
- 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
- Kruskall-Wallis
- 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, 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, Confounders controlled for: "dietary influence" 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.dietary influence, Confounders controlled for: "antibiotic treatment" 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.antibiotic treatment
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
Source: Figure 5D
Description: Relative abundance of Firmicute in the LF vs HF
Abundance in Group 1: increased abundance in High-Fat Diet (HF) group
Experiment 2
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Low-Fat Diet with Excretory-secretory products (LFE) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes mice fed a LF diet (5% fat by weight) and intraperitoneally injected with 200 μl vehicle control added with 20 μg ESPs twice a week.
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 2
Source: Figure 5E
Description: Relative abundance of Bacteroidetes of the HF and LF
Abundance in Group 1: decreased abundance in Low-Fat Diet with Excretory-secretory products (LFE) group
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HF
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HFE
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes mice receiving the HF diet (60% fat by weight) and intraperitoneally injected with 200 μl vehicle control which was added with 20 μg ESPs twice a week as the HFE group
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
Source: 5K
Description: Comparison of the representative taxonomic abundance of Proteobacteria among the LF, LFE, HF, and HFE groups at the class, order and family levels.
Abundance in Group 1: increased abundance in HFE
| NCBI | Quality Control | Links |
|---|---|---|
| Deltaproteobacteria | ||
| Desulfovibrionales |
Revision editor(s): Joiejoie
Signature 2
Source: Figure 5K
Description: Comparison of the representative taxonomic abundance of Proteobacteria among the LF, LFE, HF, and HFE groups at the class, order and family levels.
Abundance in Group 1: decreased abundance in HFE
| NCBI | Quality Control | Links |
|---|---|---|
| Desulfovibrionaceae |
Revision editor(s): Joiejoie
Experiment 4
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- HFE
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HF
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes mice receiving the HF diet (60% fat by weight) and intraperitoneally injected with 200 μl vehicle control twice a week.
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
Source: Figure 5L
Description: Comparison of the representative taxonomic abundance of Bacteroidetes among the LF, LFE, HF, and HFE groups at the genus level.
Abundance in Group 1: increased abundance in HF
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerovorax | ||
| Ileibacterium_valensIleibacterium_valens |
Revision editor(s): Joiejoie
Signature 2
Source: Figure 5L
Description: Comparison of the representative taxonomic abundance of Bacteroidetes among the LF, LFE, HF, and HFE groups at the genus level.
Abundance in Group 1: decreased abundance in HF
| NCBI | Quality Control | Links |
|---|---|---|
| Odoribacter | ||
| Romboutsia | ||
| Lactobacillus_intesinalisLactobacillus_intesinalis |
Revision editor(s): Joiejoie
Experiment 5
Differences from previous experiment shown
Subjects
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- HFE + AB
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group includes mice from the HFE group given a cocktail of antibiotics (HFE+Ab) in the drinking water to investigate the role of gut microbiota in ESPs intervention.
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- body weight, 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, Confounders controlled for: "antibiotic treatment" 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.antibiotic treatment, Confounders controlled for: "dietary treatment" 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.dietary treatment
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
Source: Figure S6
Description: Antibiotics significantly decreased bacterial DNA of faces in HFE mice
Abundance in Group 1: decreased abundance in HFE + AB
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteria |
Revision editor(s): Joiejoie
Signature 2
Source: Figure S6
Description: ESPs supplementation in HF (HFE) group and ESPs supplement with antibiotics (HFE+AB) group
Abundance in Group 1: decreased abundance in HFE + AB
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteria |
Revision editor(s): Joiejoie
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