The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet
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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
Olson CA, Vuong HE, Yano JM, Liang QY, Nusbaum DJ, Hsiao EY
Journal
Cell
Year
2018
Keywords:
6-Hz seizures, Akkermansia, GGsTop, Kcna1, Parabacteroides, epilepsy, gamma-glutamyl transpeptidase, ketogenic diet, microbiome, microbiota
The ketogenic diet (KD) is used to treat refractory epilepsy, but the mechanisms underlying its neuroprotective effects remain unclear. Here, we show that the gut microbiota is altered by the KD and required for protection against acute electrically induced seizures and spontaneous tonic-clonic seizures in two mouse models. Mice treated with antibiotics or reared germ free are resistant to KD-mediated seizure protection. Enrichment of, and gnotobiotic co-colonization with, KD-associated Akkermansia and Parabacteroides restores seizure protection. Moreover, transplantation of the KD gut microbiota and treatment with Akkermansia and Parabacteroides each confer seizure protection to mice fed a control diet. Alterations in colonic lumenal, serum, and hippocampal metabolomic profiles correlate with seizure protection, including reductions in systemic gamma-glutamylated amino acids and elevated hippocampal GABA/glutamate levels. Bacterial cross-feeding decreases gamma-glutamyltranspeptidase activity, and inhibiting gamma-glutamylation promotes seizure protection in vivo. Overall, this study reveals that the gut microbiota modulates host metabolism and seizure susceptibility in mice.
Experiment 1
Needs review
Subjects
- Location of subjects
- United States of America
- 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 ketogenic diet Response to ketogenic diet,response to ketogenic diet
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- control diet (CD) group day 14
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- ketogenic diet (KD) group day 14
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- specific-pathogen free (SPF) mice after 14 days of ketogenic diet treatment
- Group 0 sample size Number of subjects in the control (unexposed) group
- 9
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
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
- Kruskall-Wallis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
Signature 1
Needs review
Source: Figure S1D
Description: Fecal microbiome of KD group compared to CD group after 14 days of treatment
Abundance in Group 1: increased abundance in ketogenic diet (KD) group day 14
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia muciniphila | ||
| Erysipelotrichaceae | ||
| Sutterella |
Revision editor(s): Kavyaayala, WikiWorks
Signature 2
Needs review
Source: Figure S1D
Description: Fecal microbiome of KD group compared to CD group after 14 days of treatment
Abundance in Group 1: decreased abundance in ketogenic diet (KD) group day 14
| NCBI | Quality Control | Links |
|---|---|---|
| Allobaculum | ||
| Bifidobacterium | ||
| Bifidobacterium longum | ||
| Desulfovibrio |
Revision editor(s): Kavyaayala, WikiWorks
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- control diet (CD) group day 8
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- ketogenic diet (KD) group day 8
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- specific-pathogen free (SPF) mice after 8 days of ketogenic diet treatment
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure S1D
Description: Fecal microbiome of KD group compared to CD group after 8 days of treatment
Abundance in Group 1: increased abundance in ketogenic diet (KD) group day 8
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia muciniphila | ||
| Erysipelotrichaceae | ||
| Parabacteroides |
Revision editor(s): Kavyaayala, WikiWorks
Signature 2
Needs review
Source: Figure S1D
Description: Fecal microbiome of KD group compared to CD group after 8 days of treatment
Abundance in Group 1: decreased abundance in ketogenic diet (KD) group day 8
| NCBI | Quality Control | Links |
|---|---|---|
| Allobaculum | ||
| Bifidobacterium | ||
| Bifidobacterium longum | ||
| Desulfovibrio |
Revision editor(s): Kavyaayala, WikiWorks
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- control diet (CD) group day 4
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- ketogenic diet (KD) group day 4
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- specific-pathogen free (SPF) mice after 4 days of ketogenic diet treatment
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure S1D
Description: Fecal microbiome of KD group compared to CD group after 4 days of treatment
Abundance in Group 1: increased abundance in ketogenic diet (KD) group day 4
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia muciniphila | ||
| Erysipelotrichaceae | ||
| Parabacteroides |
Revision editor(s): Kavyaayala, WikiWorks
Signature 2
Needs review
Source: Figure S1D
Description: Fecal microbiome of KD group compared to CD group after 4 days of treatment
Abundance in Group 1: decreased abundance in ketogenic diet (KD) group day 4
| NCBI | Quality Control | Links |
|---|---|---|
| Desulfovibrio |
Revision editor(s): Kavyaayala, WikiWorks
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Kcna1−/− control diet (CD) group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Kcna1−/− ketogenic diet (KD) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Kcna1−/− SPF mice treated with Abx or vehicle for 1 week, gavaged with vehicle or A. muciniphila and Parabacteroides, and fed KD or CD for 3 weeks. Kcna1−/− group is used to mimic a gene mutation in humans that causes neurological problems such as epilepsy.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 21
- Group 1 sample size Number of subjects in the case (exposed) group
- 21
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure 5B
Description: Fecal microbiome of Kcna1−/− KD group mice compared to Kcna1−/− CD group mice
Abundance in Group 1: increased abundance in Kcna1−/− ketogenic diet (KD) group
| NCBI | Quality Control | Links |
|---|---|---|
| Akkermansia muciniphila | ||
| Parabacteroides |
Revision editor(s): Kavyaayala
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