The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet

Study information

Needs review

study design

randomized controlled trial

Citation

PMID PubMed identifier for scientific articles.

29804833

DOI Digital object identifier for electronic documents.

10.1016/j.cell.2018.04.027

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

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Needs review

Curated date: 2024/12/12

Curator: Kavyaayala

Revision editor(s): Kavyaayala

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

Group 1 name Corresponds to the case (exposed) group for case-control studies: ketogenic diet (KD) group

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: 3-4 week old specific-pathogen free (SPF) mice with 6 Hz induced seizures undergoing ketogenic diet treatment

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