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

Study information

Needs review

study design

time series / longitudinal observational

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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Needs review

Curated date: 2024/12/17

Curator: Kavyaayala

Revision editor(s): Kavyaayala

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: pre-KD SE rats

Group 1 name Corresponds to the case (exposed) group for case-control studies: post-KD SE rats

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: rats with status epilepticus after having undergone ketogenic diet therapy

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