The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy

Marie Lindefeldt, Alexander Eng, Hamid Darban, Annelie Bjerkner, Cecilia K. Zetterström, Tobias Allander, Björn Andersson, Elhanan Borenstein, Maria Dahlin, Stefanie Prast-Nielsen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


The gut microbiota has been linked to various neurological disorders via the gut–brain axis. Diet influences the composition of the gut microbiota. The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet established for treatment of therapy-resistant epilepsy in children. Its efficacy in reducing seizures has been confirmed, but the mechanisms remain elusive. The diet has also shown positive effects in a wide range of other diseases, including Alzheimer’s, depression, autism, cancer, and type 2 diabetes. We collected fecal samples from 12 children with therapy-resistant epilepsy before starting KD and after 3 months on the diet. Parents did not start KD and served as diet controls. Applying shotgun metagenomic DNA sequencing, both taxonomic and functional profiles were established. Here we report that alpha diversity is not changed significantly during the diet, but differences in both taxonomic and functional composition are detected. Relative abundance of bifidobacteria as well as E. rectale and Dialister is significantly diminished during the intervention. An increase in relative abundance of E. coli is observed on KD. Functional analysis revealed changes in 29 SEED subsystems including the reduction of seven pathways involved in carbohydrate metabolism. Decomposition of these shifts indicates that bifidobacteria and Escherichia are important contributors to the observed functional shifts. As relative abundance of health-promoting, fiber-consuming bacteria becomes less abundant during KD, we raise concern about the effects of the diet on the gut microbiota and overall health. Further studies need to investigate whether these changes are necessary for the therapeutic effect of KD.

Original languageEnglish
Article number5
Journalnpj Biofilms and Microbiomes
Issue number1
StatePublished - 1 Dec 2019


FundersFunder number
Karolinska Institutets Research Funds
Margarethahemmet Society
Stiftelsen Sunnerdahls Handikappfond, Linnea & Josef Carlssons Foundation
Stockholm County Council Research Funds
National Institutes of Health
National Institute of General Medical SciencesR01GM124312
Knut och Alice Wallenbergs Stiftelse
Science for Life Laboratory


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