Parasite-Derived Excretory-Secretory Products Alleviate Gut Microbiota Dysbiosis and Improve Cognitive Impairment Induced by a High-Fat Diet

From BugSigDB
Needs review
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

Curated date: 2024/10/30

Curator: Joiejoie

Revision editor(s): Joiejoie, Chloe, MyleeeA

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
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
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
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): Joiejoie, MyleeeA

Source: Figure 5i

Description: Linear discriminant analysis (LDA) effect size (LEfSe) showing the most differentially significant abundant taxa enriched in microbiota from the High Fat diet-fed (HF) vs. Low Fat diet-fed (LF).

Abundance in Group 1: increased abundance in High-Fat Diet (HF) group

NCBI Quality ControlLinks
Bacillota
Clostridia
Deltaproteobacteria
Desulfovibrionaceae
Desulfovibrionales
Eubacteriales
Faecalibaculum
Lachnospiraceae
Oscillospiraceae
Pseudomonadota
Thomasclavelia
Ruminiclostridium

Revision editor(s): Joiejoie, MyleeeA

Signature 2

Needs review

Curated date: 2024/11/04

Curator: Joiejoie

Revision editor(s): Joiejoie, MyleeeA

Source: Figure 5

Description: Linear discriminant analysis (LDA) effect size (LEfSe) showing the most differentially significant abundant taxa enriched in microbiota from the High Fat diet-fed (HF) vs. Low Fat diet-fed (LF).

Abundance in Group 1: decreased abundance in High-Fat Diet (HF) group

NCBI Quality ControlLinks
Bacteroidia
Bacteroidota
Bacteroidales
Muribaculaceae
Parabacteroides
Parasutterella

Revision editor(s): Joiejoie, MyleeeA

Experiment 2


Needs review

Curated date: 2024/11/13

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
High-Fat Diet (HF) group
Group 1 name Corresponds to the case (exposed) 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
Mice receiving the HF diet (60% fat by weight) and intraperitoneally injected with 200 ml vehicle control which was added with 20 mg Excretory-secretory products (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 1

Needs review

Curated date: 2024/11/13

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 5j

Description: Linear discriminant analysis (LDA) effect size (LEfSe) showing the most differentially significant abundant taxa enriched in microbiota from the High-Fat Diet with Excretory-secretory products (HFE) group vs. High Fat diet-fed (HF).

Abundance in Group 1: increased abundance in High-Fat Diet with Excretory-secretory products (HFE) group

NCBI Quality ControlLinks
Odoribacter
Romboutsia
unclassified Eubacteriales
Lactobacillus intestinalis

Revision editor(s): MyleeeA

Signature 2

Needs review

Curated date: 2024/11/13

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 5j

Description: Linear discriminant analysis (LDA) effect size (LEfSe) showing the most differentially significant abundant taxa enriched in microbiota from the High-Fat Diet with Excretory-secretory products (HFE) group vs. High Fat diet-fed (HF).

Abundance in Group 1: decreased abundance in High-Fat Diet with Excretory-secretory products (HFE) group

NCBI Quality ControlLinks
Anaerovorax
Ileibacterium valens
Ileibacterium
Hungateiclostridiaceae bacterium KB18
Dorea
Dorea longicatena
[Clostridium] leptum
Lachnospiraceae
Desulfovibrionaceae
Desulfovibrionales
Deltaproteobacteria
Pseudomonadota

Revision editor(s): MyleeeA