The Gut Microbiota Mediates the Anti-Seizure Effects of the Ketogenic Diet
| Autor: | Christine A. Olson, Helen E. Vuong, Elaine Y. Hsiao, Qingxing Y. Liang, Jessica Yano, David J. Nusbaum |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_treatment Glutamic Acid Pharmacology Gut flora Hippocampus Neuroprotection General Biochemistry Genetics and Molecular Biology Article Feces Mice 03 medical and health sciences Epilepsy 0302 clinical medicine Intestinal mucosa Seizures RNA Ribosomal 16S medicine Animals Bacteroides Intestinal Mucosa gamma-Aminobutyric Acid Mice Knockout Mice Inbred C3H Principal Component Analysis biology Glutamate receptor Akkermansia gamma-Glutamyltransferase biology.organism_classification medicine.disease Anti-Bacterial Agents Gastrointestinal Microbiome Transplantation Disease Models Animal 030104 developmental biology Metabolome Diet Ketogenic Kv1.1 Potassium Channel 030217 neurology & neurosurgery Ketogenic diet |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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