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

The gut microbiota has been linked to various neurological disorders via the gut-brain-axis. Diet, in turn, 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 three months on the diet. Parents did not start KD and served as diet controls. Applying shotgun metagenomic DNA sequencing we established both taxonomic and functional profiles. While alpha diversity was not changed significantly during the diet, differences in both taxonomic and functional composition were detected. Bifidobacteria were significantly diminished during the intervention as well as E. rectale and Dialister. An increase in E. coli was 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 indicated that bifidobacteria and Escherichia were important contributors to the observed functional shifts. As health-promoting, fiber-consuming bacteria become 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.