Gut flora and metabolism are altered in epilepsy and partially restored after ketogenic diets
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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 Uniform resource identifier for web resources.
Authors
Gong X, Cai Q, Liu X, An D, Zhou D, Luo R, Peng R, Hong Z
Journal
Microbial pathogenesis
Year
2021
Keywords:
16S RNA sequence, Epilepsy, Fecal microbiota, Ketogenic diets, Short chain fatty acids
OBJECTIVE: The aim of this study was to investigate the composition of the intestinal microbiota and its association with fecal short chain fatty acids (SCFAs) in children with drug refractory epilepsy (DRE) before and after treatment with a ketogenic diet (KD). METHODS: Herein, we conducted a cross-sectional study of 12 children with DRE and 12 matched healthy controls to compare the changes in fecal microbiomes and SCFAs. Disease cohort also underwent analysis before and after 6 months of KD treatment. RESULTS: A higher microbial alpha diversity and a significant increase in Actinobacteria at the phylum level and Enterococcus, Anaerostipes, Bifidobacterium, Bacteroides, and Blautia at the genus level were observed in the children with DRE. The abundance of the eight epileptic-associated genera was reversed after six months of KD treatment with decreases in Bifidobacterium, Akkermansia, Enterococcaceae and Actinomyces and increases in Subdoligranulum, Dialister, Alloprevotella (p < 0.05). In particular, we identified some taxa that were more prevalent in patients with an inadequate response to KD than in those with an adequate response. Further, a significant correlation was observed between the change in the microbiome genera after KD treatment. The SCFA content in the fecal after 6 months of KD treatment increased and was highly correlated with the gut bacteria. SIGNIFICANCES: Dysbiosis of the microbiome could be involved in the pathogenesis of DRE in children, which can be relieved by a KD to a large extent. Gut microbiota and microbial metabolism could contribute to the antiseizure effect of KD.
Experiment 1
Needs review
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- 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
- Epilepsy [X]Other epilepsy,[X]Other epilepsy (disorder),EF - Epileptic fit,EP - Epilepsy,Epilectic attack, NOS,EPILEP NEC W/O INTR EPIL,EPILEP NOS W/O INTR EPIL,epilepsy,Epilepsy (disorder),Epilepsy and recurrent seizures,EPILEPSY NEC W INTR EPIL,Epilepsy NOS,Epilepsy NOS (disorder),EPILEPSY NOS W INTR EPIL,Epilepsy, NOS,Epilepsy, unspecified,Epilepsy, unspecified, with intractable epilepsy,Epilepsy, unspecified, without mention of intractable epilepsy,Epileptic,Epileptic attack,Epileptic attack, NOS,Epileptic convulsions,Epileptic convulsions, NOS,Epileptic disorder,Epileptic disorder, NOS,Epileptic fit,Epileptic fits,Epileptic fits, NOS,Epileptic Seizure,Epileptic seizure (finding),Epileptic seizures,Epileptic seizures, NOS,Generalised convulsion,Generalised fit,Generalised seizure,Generalized convulsion,Generalized fit,Generalized seizure,Generalized seizure (finding),Other forms of epilepsy,Other forms of epilepsy (disorder),Other forms of epilepsy and recurrent seizures,Other forms of epilepsy NOS,Other forms of epilepsy NOS (disorder),Other forms of epilepsy, with intractable epilepsy,Other forms of epilepsy, without mention of intractable epilepsy,Seizure disorder,seizure disorder,Seizure disorder (disorder),Epilepsy
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy Controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Pre-ketogenic diet (KD1)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children with drug refractory epilepsy (DRE) before ketogenic diet (KD) treatment
- 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)
- 3 months
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
- 4
- Matched on Factors on which subjects have been matched on in a case-control study
- age, Matched on: "gender" 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.gender
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Figure 2
Description: Fecal microbiome of (pre-ketogenic diet) KD1 group compared to Healthy controls
Abundance in Group 1: increased abundance in Pre-ketogenic diet (KD1)
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Signature 2
Needs review
Source: Figure 2
Description: Fecal microbiome of (pre-ketogenic diet) KD1 group compared to Healthy controls
Abundance in Group 1: decreased abundance in Pre-ketogenic diet (KD1)
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridia | ||
| Eubacteriales | ||
| Oscillospiraceae |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to ketogenic diet Response to ketogenic diet,response to ketogenic diet
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Post-ketogenic diet (KD2)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children with drug refractory epilepsy (DRE) after ketogenic diet (KD) treatment
Lab analysis
Statistical Analysis
- Statistical test
- Mann-Whitney (Wilcoxon)
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Figure 4E-H
Description: Fecal microbiome of (Post-ketogenic diet) KD2 group compared to Healthy controls
Abundance in Group 1: decreased abundance in Post-ketogenic diet (KD2)
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| Dialister | ||
| Subdoligranulum | ||
| unclassified Ruminococcus |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Signature 2
Needs review
Source: Figure 4A-D
Description: Fecal microbiome of (Post-ketogenic diet) KD2 group compared to Healthy controls
Abundance in Group 1: increased abundance in Post-ketogenic diet (KD2)
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces | ||
| Akkermansia | ||
| Enterococcus |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Epilepsy [X]Other epilepsy,[X]Other epilepsy (disorder),EF - Epileptic fit,EP - Epilepsy,Epilectic attack, NOS,EPILEP NEC W/O INTR EPIL,EPILEP NOS W/O INTR EPIL,epilepsy,Epilepsy (disorder),Epilepsy and recurrent seizures,EPILEPSY NEC W INTR EPIL,Epilepsy NOS,Epilepsy NOS (disorder),EPILEPSY NOS W INTR EPIL,Epilepsy, NOS,Epilepsy, unspecified,Epilepsy, unspecified, with intractable epilepsy,Epilepsy, unspecified, without mention of intractable epilepsy,Epileptic,Epileptic attack,Epileptic attack, NOS,Epileptic convulsions,Epileptic convulsions, NOS,Epileptic disorder,Epileptic disorder, NOS,Epileptic fit,Epileptic fits,Epileptic fits, NOS,Epileptic Seizure,Epileptic seizure (finding),Epileptic seizures,Epileptic seizures, NOS,Generalised convulsion,Generalised fit,Generalised seizure,Generalized convulsion,Generalized fit,Generalized seizure,Generalized seizure (finding),Other forms of epilepsy,Other forms of epilepsy (disorder),Other forms of epilepsy and recurrent seizures,Other forms of epilepsy NOS,Other forms of epilepsy NOS (disorder),Other forms of epilepsy, with intractable epilepsy,Other forms of epilepsy, without mention of intractable epilepsy,Seizure disorder,seizure disorder,Seizure disorder (disorder),Epilepsy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Pre-ketogenic diet (KD1)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children with (drug refractory epilepsy) DRE before (ketogenic diet) KD treatment
Lab analysis
Statistical Analysis
Alpha Diversity
- Chao1 Abundance-based estimator of species richness
- increased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- unchanged
Signature 1
Needs review
Source: Figures 4A-D & 5A-C
Description: Fecal microbiome of (pre-ketogenic diet) KD1 group compared to Healthy controls
Abundance in Group 1: increased abundance in Pre-ketogenic diet (KD1)
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces | ||
| Akkermansia | ||
| Bacteroides | ||
| Bifidobacterium | ||
| Enterococcus | ||
| Mycoplasmatota |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Signature 2
Needs review
Source: Figures 4E-G & 5E-F
Description: Fecal microbiome of (pre-ketogenic diet) KD1 group compared to Healthy controls
Abundance in Group 1: decreased abundance in Pre-ketogenic diet (KD1)
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| Dialister | ||
| Subdoligranulum | ||
| unclassified Christensenellaceae |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Experiment 5
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to ketogenic diet Response to ketogenic diet,response to ketogenic diet
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy Controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- KD2 (post-ketogenic diet) responders
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children with (drug refractory epilepsy) DRE who were classified as having seizure reduction frequency greater than or equal to 50% after (ketogenic diet) KD treatment. Samples analyzed from (post-ketogenic diet) KD2 group.
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure 5D-F
Description: Fecal microbiome of (post-ketogenic diet) KD2 responders compared to Healthy controls
Abundance in Group 1: decreased abundance in KD2 (post-ketogenic diet) responders
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| unclassified Christensenellaceae | ||
| unclassified Ruminococcus |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Experiment 6
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- KD2 (Post-ketogenic diet) non responders
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- KD2 (Post-ketogenic diet) responders
- Group 0 sample size Number of subjects in the control (unexposed) group
- 4
Lab analysis
Statistical Analysis
- Matched on Factors on which subjects have been matched on in a case-control study
- Not specified
Signature 1
Needs review
Source: Results Section 3.3 (Text)
Description: Fecal microbiome of (Post-ketogenic diet) KD2 responders compared to (Post-ketogenic diet) KD2 non responders
Abundance in Group 1: increased abundance in KD2 (Post-ketogenic diet) responders
| NCBI | Quality Control | Links |
|---|---|---|
| Dialister | ||
| Eubacterium |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Experiment 7
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- KD1 (Pre-ketogenic diet) without gene mutation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- KD2 (Post-ketogenic diet) without gene mutation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children with (drug refractory epilepsy) DRE and without gene mutation after KD (ketogenic diet) treatment
- 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
Lab analysis
Statistical Analysis
- Statistical test
- LEfSe
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 4
Signature 1
Needs review
Source: Results Section 3.3 (Text)
Description: Fecal microbiome of KD2 (Post-ketogenic diet) children without gene mutation compared to KD1 (Pre-ketogenic diet) children without gene mutation
Abundance in Group 1: increased abundance in KD2 (Post-ketogenic diet) without gene mutation
| NCBI | Quality Control | Links |
|---|---|---|
| Hungatella |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Signature 2
Source: Results Section 3.3 (Text)
Description: Fecal microbiome of KD2 (Post-ketogenic diet) children without gene mutation compared to KD1 (Pre-ketogenic diet) children without gene mutation
Abundance in Group 1: decreased abundance in KD2 (Post-ketogenic diet) without gene mutation
| NCBI | Quality Control | Links |
|---|---|---|
| Dactylosporangium |
Revision editor(s): Tosin
Experiment 8
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- KD1 (Pre-ketogenic diet) with gene mutation
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- KD2 (Post-ketogenic diet) with gene mutation
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children with (drug refractory epilepsy) DRE and gene mutation after KD (ketogenic diet) treatment
- Group 0 sample size Number of subjects in the control (unexposed) group
- 5
- Group 1 sample size Number of subjects in the case (exposed) group
- 5
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Results Section 3.3 (Text)
Description: Fecal microbiome of (Post-ketogenic diet) KD2 children with gene mutation compared to (Pre-ketogenic diet) KD1 children with gene mutation
Abundance in Group 1: increased abundance in KD2 (Post-ketogenic diet) with gene mutation
| NCBI | Quality Control | Links |
|---|---|---|
| Parabacteroides |
Revision editor(s): Kavyaayala, WikiWorks, Tosin
Signature 2
Source: Results Section 3.3 (Text)
Description: Fecal microbiome of (Post-ketogenic diet) KD2 children with gene mutation compared to (Pre-ketogenic diet) KD1 children with gene mutation
Abundance in Group 1: decreased abundance in KD2 (Post-ketogenic diet) with gene mutation
| NCBI | Quality Control | Links |
|---|---|---|
| Sulfurospirillum | ||
| Tannerella |
Revision editor(s): Tosin
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