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

Study information

Needs review

study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

34745091

DOI Digital object identifier for electronic documents.

10.3389/fimmu.2021.710513

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

Edit History Delete

Mark reviewed

Your review change was submittedDuplicate this Experiment Add a new Signature

Needs review

Curated date: 2024/10/30

Curator: Joiejoie

Revision editor(s): Joiejoie, Chloe

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: Colon Hindgut,Large bowel,Posterior intestine,Colon,colon

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Cognitive impairment measurement , High fat diet Cognitive impairment measurement,cognitive impairment measurement,HF - High fat diet,High fat diet (finding),High fat diet,high fat diet

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Low-Fat (LF) group

Group 1 name Corresponds to the case (exposed) group for case-control studies: High-Fat Diet with Excretory-Secretory Products (HEF) group

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: In the study, Group 1, which corresponds to the case (exposed) group, is defined by the following diagnostic criteria: Condition: Mice were subjected to a high-fat diet (HF diet), specifically containing 60% fat by weight. Exposure: This group received intraperitoneal injections of 20 mg of excretory-secretory products (ESPs) derived from Echinococcus granulosus twice a week. The specific phenotype represented in this group includes cognitive impairment, which was assessed through various behavioral tests such as nest building, object location, novel object recognition, temporal order memory, and Y-maze memory tests. The study aimed to evaluate how the ESPs could mitigate the cognitive decline associated with the high-fat diet-induced neuroinflammation and gut microbiota dysbiosis.

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

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): In the study, the antibiotics exclusion criteria involved administering a cocktail of antibiotics to specific groups of mice. The key details regarding antibiotic usage are as follows: Duration Without Antibiotics: Mice in the antibiotic-treated groups were given antibiotics starting two days prior to the initiation of the high-fat diet. This indicates that there was a 2-day period without antibiotics before the dietary intervention began. Antibiotic Composition: The antibiotic cocktail included: Ampicillin (1 g/L) Vancomycin (0.25 g/L) Neomycin (1 g/L) Metronidazole (1 g/L) Fresh Preparation: The antibiotic solution was prepared fresh every 3 days during the treatment period. These criteria were used to assess the role of gut microbiota in the effects of excretory-secretory products (ESPs) on cognitive impairment and microbiota dysbiosis in the experimental model.

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).: log transformation

Statistical test: ANOVA; Kruskall-Wallis; 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)?: Yes

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2.0

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 intervention" 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 intervention, 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: increased

Simpson Estimator of species richness and species evenness: more weight on species evenness: increased

Signature 1

Edit History Delete

Mark reviewed

Your review change was submitted

Needs review

Curated date: 2024/11/04

Curator: Joiejoie

Revision editor(s): Joiejoie

Source: Frontiers in Immunology

Description: The study investigates the effects of excretory-secretory products (ESPs) derived from Echinococcus granulosus on cognitive function and gut microbiota in obese mice. Conducted by Wu et al., the research demonstrates that supplementation with ESPs can prevent cognitive decline associated with a high-fat diet by reducing neuroinflammation and restoring gut microbiota balance. Key findings include: ESPs improved cognitive performance in various behavioral tests. They suppressed neuroinflammatory responses in critical brain regions, such as the hippocampus and prefrontal cortex. ESPs reversed gut barrier dysfunction and alleviated microbiota dysbiosis caused by a high-fat diet. This study suggests that parasite-derived molecules could serve as potential therapeutic agents for obesity-related cognitive impairments, highlighting the intricate connection between gut health and brain function.

Abundance in Group 1: increased abundance in High-Fat Diet with Excretory-Secretory Products (HEF) group

NCBI	Quality Control	Links

Revision editor(s): Joiejoie