Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet

Authors

Maria Dahlin, Neuropediatric Department, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden.
Stephanie S. Singleton, School of Medicine and Health Sciences, Department of Biochemistry and Molecular Medicine, The George Washington University, HIVE Lab, Washington, D.C. 20037, USA.
John A. David, Department of Applied Mathematics, Virginia Military Institute, Lexington, VA 24450, USA.
Atin Basuchoudhary, Department of Applied Mathematics, Virginia Military Institute, Lexington, VA 24450, USA.
Ronny Wickström, Neuropediatric Department, Astrid Lindgren Children's Hospital, Karolinska Hospital, Stockholm, Sweden.
Raja Mazumder, School of Medicine and Health Sciences, Department of Biochemistry and Molecular Medicine, The George Washington University, HIVE Lab, Washington, D.C. 20037, USA.
Stefanie Prast-Nielsen, Centre for Translational Microbiome Research (CTMR), Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. Electronic address: stefanie.prast-nielsen@ki.se.

Document Type

Journal Article

Publication Date

6-1-2022

Journal

EBioMedicine

Volume

80

DOI

10.1016/j.ebiom.2022.104061

Keywords

Bifidobacterium; Bioinformatics; Epilepsy; Gut microbiota; Inflammation; Ketogenic diet; Machine learning; Omics; TNF

Abstract

BACKGROUND: Recently, studies have suggested a role for the gut microbiota in epilepsy. Gut microbial changes during ketogenic diet (KD) treatment of drug-resistant epilepsy have been described. Inflammation is associated with certain types of epilepsy and specific inflammation markers decrease during KD. The gut microbiota plays an important role in the regulation of the immune system and inflammation. METHODS: 28 children with drug-resistant epilepsy treated with the ketogenic diet were followed in this observational study. Fecal and serum samples were collected at baseline and three months after dietary intervention. FINDINGS: We identified both gut microbial and inflammatory changes during treatment. KD had a general anti-inflammatory effect. Novel bioinformatics and machine learning approaches identified signatures of specific Bifidobacteria and TNF (tumor necrosis factor) associated with responders before starting KD. During KD, taxonomic and inflammatory profiles between responders and non-responders were more similar than at baseline. INTERPRETATION: Our results suggest that children with drug-resistant epilepsy are more likely to benefit from KD treatment when specific Bifidobacteria and TNF are elevated. We here present a novel signature of interaction of the gut microbiota and the immune system associated with anti-epileptic response to KD treatment. This signature could be used as a prognostic biomarker to identify potential responders to KD before starting treatment. Our findings may also contribute to the development of new anti-seizure therapies by targeting specific components of the gut microbiota. FUNDING: This study was supported by the Swedish Brain Foundation, Margarethahemmet Society, Stiftelsen Sunnerdahls Handikappfond, Linnea & Josef Carlssons Foundation, and The McCormick Genomic & Proteomic Center.

APA Citation

Dahlin, Maria; Singleton, Stephanie S.; David, John A.; Basuchoudhary, Atin; Wickström, Ronny; Mazumder, Raja; and Prast-Nielsen, Stefanie, "Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet" (2022). GW Authored Works. Paper 1184.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1184

Department

Biochemistry and Molecular Medicine