Cross talk between drug-resistant epilepsy and the gut microbiome.


Journal

Epilepsia
ISSN: 1528-1167
Titre abrégé: Epilepsia
Pays: United States
ID NLM: 2983306R

Informations de publication

Date de publication:
12 2020
Historique:
received: 22 07 2020
revised: 16 09 2020
accepted: 07 10 2020
pubmed: 4 11 2020
medline: 4 3 2021
entrez: 3 11 2020
Statut: ppublish

Résumé

One-third of epilepsy patients have drug-resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut-brain-axis are likely to shed light on epilepsy pathogenesis, anti-seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood-brain barrier disruption, and altered neuromodulators. High-throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug-sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low-carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition varies between diet responders and nonresponders. Murine models suggest that specific phyla are necessary to confer efficacy from the diet, and antibiotic treatment may eliminate efficacy. The impact of diet might involve alterations in microbiota, promotion of select microbial interactions, and variance in brain neurotransmitter levels that then influence seizures. Understanding the mechanics of how diet manipulates seizures may suggest novel therapies. Most ASMs act on neuronal transmission via effects on ion channels and neurotransmitters. However, ASMs may also assert their effects via the gut microbiota. In animal models, the microbiota composition (eg, abundance of certain phyla) can vary with ASM active drug metabolites. Given the developing understanding of the gut microbiome in DRE, probiotics are another potential therapy. Probiotics alter the microbiota composition, and small studies suggest that these supplements can reduce seizures in some patients. DRE has enormous consequences to patients and society, and the gut microbiome holds promise as a potential therapeutic target. However, the exact mechanism and recognition of which patients are likely to be responders remain elusive. Further studies are warranted.

Identifiants

pubmed: 33140419
doi: 10.1111/epi.16744
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

2619-2628

Subventions

Organisme : FACES

Informations de copyright

© 2020 International League Against Epilepsy.

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Auteurs

Manisha Holmes (M)

NYU Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Health, New York, NY, USA.

Zia Flaminio (Z)

Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA.

Mridula Vardhan (M)

Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA.

Fangxi Xu (F)

Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA.

Xin Li (X)

Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA.

Orrin Devinsky (O)

NYU Comprehensive Epilepsy Center, Department of Neurology, New York University Langone Health, New York, NY, USA.

Deepak Saxena (D)

Department of Molecular Pathobiology, New York University College of Dentistry and Department of Surgery, New York University School of Medicine, New York, NY, USA.

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