Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation
From BugSigDB
Jump to:navigation, search
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
Wang X, Wang Z, Cao J, Dong Y, Chen Y
Journal
Microbiome
Year
2023
Keywords:
Cognitive impairment, Hippocampus, Melatonin, Microbial–gut–brain axis, Sleep deprivation
Sleep loss is a serious global health concern. Consequences include memory deficits and gastrointestinal dysfunction. Our previous research showed that melatonin can effectively improve cognitive impairment and intestinal microbiota disturbances caused by sleep deprivation (SD). The present study further explored the mechanism by which exogenous melatonin prevents SD-induced cognitive impairments. Here, we established fecal microbiota transplantation, Aeromonas colonization and LPS or butyrate supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in melatonin in alleviating SD-induced memory impairment. RESULTS: Transplantation of the SD-gut microbiota into normal mice induced microglia overactivation and neuronal apoptosis in the hippocampus, cognitive decline, and colonic microbiota disorder, manifesting as increased levels of Aeromonas and LPS and decreased levels of Lachnospiraceae_NK4A136 and butyrate. All these events were reversed with the transplantation of SD + melatonin-gut microbiota. Colonization with Aeromonas and the addition of LPS produced an inflammatory response in the hippocampus and spatial memory impairment in mice. These changes were reversed by supplementation with melatonin, accompanied by decreased levels of Aeromonas and LPS. Butyrate administration to sleep-deprived mice restored inflammatory responses and memory impairment. In vitro, LPS supplementation caused an inflammatory response in BV2 cells, which was improved by butyrate supplementation. This ameliorative effect of butyrate was blocked by pretreatment with MCT1 inhibitor and HDAC3 agonist but was mimicked by TLR4 and p-P65 antagonists. CONCLUSIONS: Gut microbes and their metabolites mediate the ameliorative effects of melatonin on SD-induced cognitive impairment. A feasible mechanism is that melatonin downregulates the levels of Aeromonas and constituent LPS and upregulates the levels of Lachnospiraceae_NK4A136 and butyrate in the colon. These changes lessen the inflammatory response and neuronal apoptosis in the hippocampus through crosstalk between the TLR4/NF-κB and MCT1/ HDAC3 signaling pathways. Video Abstract.
Experiment 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-12
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 transplant Response to transplant,response to transplant
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- SD-FMT AND SD+MEL-FMT
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CON-FMT: receiving control microbiota FMT mice
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- FMT administered mice without sleep deprivation.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 7
- Group 1 sample size Number of subjects in the case (exposed) group
- 7
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- There were no antibiotic exclusions
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V1-V9
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- PacBio RS
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
- 3.0
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-12
Curated date: 2023/10/13
Curator: Davvve
Revision editor(s): Davvve, Chinelsy, Peace Sandy, Folakunmi
Source: fig 4
Description: Difference between the gut microbiome of the CON- FNT and the SD-FMT groups by LEFse
Abundance in Group 1: increased abundance in CON-FMT: receiving control microbiota FMT mice
Revision editor(s): Davvve, Chinelsy, Peace Sandy, Folakunmi
Experiment 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-12
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CON-FMT:( receiving control microbiota FMT mice) and SD+Mel-FMT:( receiving SD+Mel (20 mg/kg) microbiota FMT mice)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- SD-FMT: receiving Sleep deprivation FMT mice
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This are sleep deprived mice that are also subjected to FMT .
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- There were no antibiotic
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-12
Source: Fig 4C, 4F, 4D
Description: C Linear discriminant analysis efect size (LEfSe) was performed to identify the bacteria that are differentially represented between the different groups
Abundance in Group 1: increased abundance in SD-FMT: receiving Sleep deprivation FMT mice
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-2-12
Source: Fig 4G-J
Description: Linear discriminant analysis effect size (LEfSe) performed to identify the bacteria that are differentially represented between the different groups
Abundance in Group 1: decreased abundance in SD-FMT: receiving Sleep deprivation FMT mice
| NCBI | Quality Control | Links |
|---|---|---|
| Eubacterium xylanophilum | ||
| Lachnospiraceae bacterium NK4A136 | ||
| Ruminococcus | ||
| Lachnospiraceae bacterium A2 |
Revision editor(s): Folakunmi
Experiment 3
Reviewed Marked as Reviewed by Folakunmi on 2024-2-12
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CON-FMT and SD-FMT
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- SD+Mel-FMT:( receiving SD+Mel (20 mg/kg) microbiota FMT mice)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Sleep deprived mice receiving Mel and FMT
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- There were no antibiotics exclusions from this study
Lab analysis
Statistical Analysis
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- unchanged
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-2-12
Source: fig 4c
Description: Linear discriminant analysis efect size (LEfSe) was performed to identify the bacteria that are differentially represented between the different groups
Abundance in Group 1: increased abundance in SD+Mel-FMT:( receiving SD+Mel (20 mg/kg) microbiota FMT mice)
Revision editor(s): Davvve
Retrieved from "https://bugsigdb.org/w/index.php?title=Study_804&oldid=115008"
