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
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-keto diet epilepsy group (KD1)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- children with drug resistant epilepsy before ketogenic diet therapy
- 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
- Mann-Whitney (Wilcoxon)
- 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: Comparing difference in fecal microbiome of children with DRE before KD treatment (KD1 group) to healthy controls
Abundance in Group 1: increased abundance in pre-keto diet epilepsy group (KD1)
Revision editor(s): Kavyaayala
Signature 2
Needs review
Source: Figure 2
Description: Comparing difference in fecal microbiome of children with DRE before KD treatment (KD1 group) to healthy controls
Abundance in Group 1: decreased abundance in pre-keto diet epilepsy group (KD1)
| NCBI | Quality Control | Links |
|---|---|---|
| Clostridia | ||
| Eubacteriales | ||
| Oscillospiraceae |
Revision editor(s): Kavyaayala
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 1 name Corresponds to the case (exposed) group for case-control studies
- post-keto diet epilepsy group (KD2)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- children with drug resistant epilepsy after six months of ketogenic diet therapy
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: Comparing difference in fecal microbiome of children with DRE after KD treatment (KD2 group) to healthy controls
Abundance in Group 1: decreased abundance in post-keto diet epilepsy group (KD2)
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| Dialister | ||
| Subdoligranulum | ||
| unclassified Ruminococcus |
Revision editor(s): Kavyaayala
Signature 2
Needs review
Source: Figure 4A-D
Description: Comparing difference in fecal microbiome of children with DRE after KD treatment (KD2 group) to healthy controls
Abundance in Group 1: increased abundance in post-keto diet epilepsy group (KD2)
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomyces | ||
| Akkermansia | ||
| Enterococcaceae |
Revision editor(s): Kavyaayala
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-keto diet epilepsy group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- children with drug resistant epilepsy before ketogenic diet therapy
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
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Ketogenic diet Ketogenic diet,ketogenic diet
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- adequate KD responders
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- inadequate KD responders
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- children with DRE who had reduction in seizure frequency of less than 50% after KD treatment
- Group 0 sample size Number of subjects in the control (unexposed) group
- 8
- Group 1 sample size Number of subjects in the case (exposed) 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: Figure 5E-F
Description: Comparing difference in fecal microbiome of children with DRE who had inadequate response to KD vs those with adequate response
Abundance in Group 1: decreased abundance in inadequate KD responders
| NCBI | Quality Control | Links |
|---|---|---|
| Alloprevotella | ||
| unclassified Christensenellaceae | ||
| unclassified Ruminococcus |
Revision editor(s): Kavyaayala
Signature 2
Needs review
Source: Figure 5A-C
Description: Comparing difference in fecal microbiome of children with DRE who had inadequate response to KD vs those with adequate response
Abundance in Group 1: increased abundance in inadequate KD responders
| NCBI | Quality Control | Links |
|---|---|---|
| Mycoplasmatota | ||
| Akkermansia | ||
| Bacteroides |
Revision editor(s): Kavyaayala
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