Ketogenic Diets Alter the Gut Microbiome, Resulting in Decreased Susceptibility to and Cognitive Impairment in Rats with Pilocarpine-Induced Status Epilepticus

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laboratory experiment
Citation
PMID PubMed identifier for scientific articles.
38935224
DOI Digital object identifier for electronic documents.
10.1007/s11064-024-04168-y
URI
Authors
Li B, Ma Y, Wang X, Zhao D, Wang Z, Wang G, Li C, Yang L, Ji H, Liu K, Chen Q, Yang Y, Ma W, Du J, Ma L, Zhang L, Qiang Y
Journal
Neurochemical research
Year
2024
Keywords:
Cognitive function, Gut microbiota, Ketogenic diet, Lithium-pilocarpine, Status epilepticus, Temporal lobe epilepsy
A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.

Experiment 1


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Curated date: 2024/12/17

Curator: Kavyaayala

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Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Rattus norvegicus
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
normal diet status epilepticus model (SE group)
Group 1 name Corresponds to the case (exposed) group for case-control studies
ketogenic diet (SE + KD group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
male rats fed ketogenic diet for three weeks before undergoing pilocarpine-induced status epilepticus
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
6

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).
relative abundances
Statistical test
ANOVA
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

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Curated date: 2024/12/17

Curator: Kavyaayala

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Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD group compared to SE group

Abundance in Group 1: increased abundance in ketogenic diet (SE + KD group)

NCBI Quality ControlLinks
Actinomycetota   
Pseudomonadota   

Revision editor(s): Kavyaayala

Signature 2

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Source: Figure 7B

Description: Difference in fecal microbiome in SE+KD group compared to SE group

Abundance in Group 1: decreased abundance in ketogenic diet (SE + KD group)

NCBI Quality ControlLinks
Bacteroidota   

Revision editor(s): Kavyaayala

Experiment 2


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Curated date: 2024/12/31

Curator: Kavyaayala

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
normal diet healthy controls (NC group)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

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Curated date: 2025/01/03

Curator: Kavyaayala

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Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD group compared to NC group

Abundance in Group 1: increased abundance in ketogenic diet (SE + KD group)

NCBI Quality ControlLinks
Actinomycetota   
Pseudomonadota   

Revision editor(s): Kavyaayala

Signature 2

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Curated date: 2025/01/03

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Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD group compared to NC group

Abundance in Group 1: decreased abundance in ketogenic diet (SE + KD group)

NCBI Quality ControlLinks
Bacteroidota   

Revision editor(s): Kavyaayala

Experiment 3


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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
normal diet controls (NC group)
Group 1 name Corresponds to the case (exposed) group for case-control studies
ketogenic diet and antibiotics (SE + KD + Ab group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
male rats fed ketogenic diet for three weeks and receiving antibiotic treatment before undergoing pilocarpine-induced status epilepticus

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete
incomplete

Curated date: 2025/01/03

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD + Ab group compared to NC group

Abundance in Group 1: increased abundance in ketogenic diet and antibiotics (SE + KD + Ab group)

NCBI Quality ControlLinks
Pseudomonadota   

Revision editor(s): Kavyaayala

Signature 2

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incomplete

Curated date: 2025/01/03

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD + Ab group compared to NC group

Abundance in Group 1: decreased abundance in ketogenic diet and antibiotics (SE + KD + Ab group)

NCBI Quality ControlLinks
Bacteroidota   

Revision editor(s): Kavyaayala

Experiment 4


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Curated date: 2025/01/03

Curator: Kavyaayala

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
ketogenic diet (SE + KD group)

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete
incomplete

Curated date: 2025/01/03

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD + Ab group compared to SE + KD group

Abundance in Group 1: increased abundance in ketogenic diet and antibiotics (SE + KD + Ab group)

NCBI Quality ControlLinks
Pseudomonadota   

Revision editor(s): Kavyaayala

Signature 2

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Curated date: 2025/01/03

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Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD + Ab group compared to SE + KD group

Abundance in Group 1: decreased abundance in ketogenic diet and antibiotics (SE + KD + Ab group)

NCBI Quality ControlLinks
Actinomycetota   

Revision editor(s): Kavyaayala

Experiment 5


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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
normal diet status epilepticus model (SE group)

Lab analysis

Statistical Analysis

Signature 1

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incomplete

Curated date: 2025/01/03

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD + Ab group compared to SE group

Abundance in Group 1: increased abundance in ketogenic diet and antibiotics (SE + KD + Ab group)

NCBI Quality ControlLinks
Pseudomonadota   

Revision editor(s): Kavyaayala

Signature 2

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incomplete

Curated date: 2025/01/03

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 7B

Description: Difference in fecal microbiome in SE + KD + Ab group compared to SE group

Abundance in Group 1: increased abundance in ketogenic diet and antibiotics (SE + KD + Ab group)

NCBI Quality ControlLinks
Bacteroidota   

Revision editor(s): Kavyaayala

Experiment 6


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Curated date: 2025/01/04

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
(SE + KD + Ab), SE, and NC groups combined
Group 1 name Corresponds to the case (exposed) group for case-control studies
ketogenic diet (SE + KD group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
male rats fed ketogenic diet for three weeks before undergoing pilocarpine-induced status epilepticus
Group 0 sample size Number of subjects in the control (unexposed) group
18

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

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Curated date: 2025/01/05

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Source: Figure 7C

Description: Difference in fecal microbiome in SE + KD group compared to (SE + KD + Ab), SE, and NC groups combined

Abundance in Group 1: increased abundance in ketogenic diet (SE + KD group)

NCBI Quality ControlLinks
Actinomycetota   
Atopobiaceae   
Blautia   
Coriobacteriales   
Coriobacteriia   
Peptococcaceae   
unclassified Blautia   
unclassified Peptococcaceae   
uncultured Allobaculum sp.   
unclassified Coriobacteriaceae UCG-002unclassified Coriobacteriaceae UCG-002
Coriobacteriaceae UCG-002Coriobacteriaceae UCG-002
Peptostreptococcales-TissierellalesPeptostreptococcales-Tissierellales
PeptococcalesPeptococcales

Revision editor(s): Kavyaayala

Experiment 7


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Curated date: 2025/01/04

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
(SE + KD + Ab), (SE + KD), and NC groups combined
Group 1 name Corresponds to the case (exposed) group for case-control studies
normal diet status epilepticus model (SE group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
male rats fed normal diet and having pilocarpine-induced status epilepticus

Lab analysis

Statistical Analysis

Signature 1

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Curated date: 2025/01/05

Curator: Kavyaayala

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Source: Figure 7C

Description: Difference in fecal microbiome in SE group compared to (SE + KD + Ab), (SE + KD), and NC groups combined

Abundance in Group 1: increased abundance in normal diet status epilepticus model (SE group)

NCBI Quality ControlLinks
Bacteroidaceae   
Bacteroides   
Christensenellaceae   
Christensenellales   
Lactobacillaceae   
Lactobacillales   
Lactobacillus   
Ligilactobacillus   
Phocaeicola sartorii   
Trichinella pseudospiralis   
unclassified Lactobacillus   
unclassified Ligilactobacillus   
Christensenellaceae R-7 groupChristensenellaceae R-7 group
UCG-005UCG-005
unclassified UCG-005unclassified UCG-005

Revision editor(s): Kavyaayala

Experiment 8


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Curated date: 2025/01/04

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
(SE + KD), SE, and NC groups combined
Group 1 name Corresponds to the case (exposed) group for case-control studies
ketogenic diet and antibiotics (SE + KD + Ab group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
male rats fed ketogenic diet for three weeks and receiving antibiotic treatment before undergoing pilocarpine-induced status epilepticus

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete
Mark reviewed
Your review change was submitted
Needs review

Curated date: 2025/01/05

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 7C

Description: Difference in fecal microbiome in SE + KD + Ab group compared to (SE + KD), SE, and NC groups combined

Abundance in Group 1: increased abundance in ketogenic diet and antibiotics (SE + KD + Ab group)

NCBI Quality ControlLinks
Coprobacillaceae   
Enterobacterales   
Enterobacteriaceae   
Erysipelotrichaceae   
Erysipelotrichales   
Flavonifractor   
Gammaproteobacteria   
Lachnoclostridium   
Oscillospiraceae   
Pseudomonadota   
unclassified Erysipelotrichaceae   
unclassified Flavonifractor   
unclassified Lachnoclostridium   
Escherichia ShigellaEscherichia Shigella
unclassified Escherichia Shigellaunclassified Escherichia Shigella
unclassified Clostridium innocuum groupunclassified Clostridium innocuum group
Clostridium innocuum groupClostridium innocuum group
Thomasclavelia   
unclassified Thomasclavelia   
unclassified Eubacterium nodatum groupunclassified Eubacterium nodatum group
Eubacterium nodatum groupEubacterium nodatum group

Revision editor(s): Kavyaayala

Experiment 9


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Curated date: 2025/01/04

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
(SE + KD + Ab), (SE + KD), and SE groups combined
Group 1 name Corresponds to the case (exposed) group for case-control studies
normal diet controls (NC group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
healthy male rats fed normal diet

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete
incomplete

Curated date: 2025/01/05

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 7C

Description: Difference in fecal microbiome in NC group compared to (SE + KD + Ab), (SE + KD), and SE groups combined

Abundance in Group 1: increased abundance in normal diet controls (NC group)

NCBI Quality ControlLinks
Bacteroidales   
Bacteroidia   
Bacteroidota   
Lachnospiraceae bacterium NK4A136   
Muribaculaceae   
Ruminococcus   
rumen bacterium NK4A214   
unclassified Muribaculaceae   
unclassified Oscillospiraceae   
unclassified Ruminococcus   
OscillospiralesOscillospirales
Clostridia UCG-014Clostridia UCG-014
unclassified Clostridia UCG-014unclassified Clostridia UCG-014

Revision editor(s): Kavyaayala

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