Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Lindefeldt M

PROVIDER: S-EPMC6344533 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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

Lindefeldt Marie M Eng Alexander A Darban Hamid H Bjerkner Annelie A Zetterström Cecilia K CK Allander Tobias T Andersson Björn B Borenstein Elhanan E Dahlin Maria M Prast-Nielsen Stefanie S

NPJ biofilms and microbiomes 20190123 1

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, auti ...[more]

PMID: 30701077

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Project description:Cerebral palsy (CP) and epilepsy are two interactive neurological diseases, and their clinical treatment can cause severe side-effects in children's development, especially when it involves long-term administration of antiepileptic drugs. Accumulating studies on the gut-brain axis indicated that the gut microbiota (GM), which participates in various neurological diseases, would provide a harmless therapeutic target for the treatment of CP and epilepsy. To explore the GM characteristics in children with both CP and epilepsy (CPE), we collected fecal samples from 25 CPE patients (CPE group) and 21 healthy children (Healthy group) for 16S rDNA sequencing. In this study, we discovered significantly higher microbial diversity in the CPE group compared to healthy group (P < 0.001). After selecting the top 15 most abundant genera in each group, we found significantly enriched Bifidobacterium, Streptococcus, Akkermansia, Enterococcus, Prevotella, Veillonella, Rothia, and Clostridium IV in the CPE group, and noticeably reduced Bacteroides, Faecalibacterium, Blautia, Ruminococcus, Roseburia, Anaerostipes, and Parasutterella. A GM co-occurrence network was also constructed, and negative correlations were discovered between Bacteroides and Lactobacillus (r = -0.768, P < 0.001, FDR < 0.001), as well as Intestinibacter and Bifidobacterium (r = -0.726, P < 0.001, FDR < 0.001). After KEGG annotation and functional enrichment, 24 functional categories exhibited different enrichment levels between the CPE and Healthy groups. The functions, associated with xenobiotics metabolism, immune system diseases, and neurodegenerative diseases, were enriched in the CPE group. Conversely, the functional categories related to the biosynthesis of secondary metabolites were reduced. Furthermore, the neurodegenerative diseases were mainly attributed to Streptococcus, while an increased risk of immune system diseases was associated with enriched Akkermansia in the CPE patients. Generally, this study characterized the GM in CPE patients, illustrated the microbial co-occurrence relationships, and detected the functional distributions of the bacteria.

Project description:The influence of gut microbiota on host immunity is widely studied, and its disturbance has been linked to several immune-mediated disorders. Conversely, whether and how inherently disturbed canonical Th1 (pro-inflammatory) and/or Th2 (anti-inflammatory) immune pathways modify the host microbiome is not sufficiently investigated. Here, we characterized the humoral, cellular, and cytokine immunity, and associated alterations in gut microbiota of naïve wild-type mice (C57BL/6 and BALB/c), and mice with deficiencies in Th2 responses (IL-4Rα and IL-33 knockout mice) or in both Th1 and Th2 responses (NOD scid gamma, NSG mice). A global analysis by de novo clustering of 16S rRNA profiles of the gut microbiota independently grouped wild-type immunocompetent (C57BL/6 and BALB/c), Th2-deficient (IL-4Rα-/- and IL-33-/-), and severely immunodeficient (NSG) mice; where wild-type mice, but not Th2 or severely immunodeficient mice, were enriched in gut bacteria that produce short-chain fatty acids. These include members of phyla Firmicutes, Verrucomicrobia, and Bacteroidetes such as Lactobacillus spp., Akkermansia muciniphila, and Odoribacter spp. Further comparison of the two naïve wild-type mouse strains showed higher microbial diversity (Shannon), primarily linked to higher richness (Chao1), as well as a distinct difference in microbial composition (weighted UniFrac) in BALB/c mice compared to C57BL/6. T-cell and blood cytokine analyses demonstrated a Th1-polarization in naïve adaptive immunity in C57BL/6 animals compared to BALB/c mice, and an expected Th2 deficient cellular response in IL-4Rα-/- and IL-33-/- mice compared to its genetic background BALB/c strain. Together, these data suggest that alterations in the Th1/Th2 balance or a complete ablation of Th1/Th2 responses can lead to major alterations in gut microbiota composition and function. Given the similarities between the human and mouse immune systems and gut microbiota, our finding that immune status is a strong driver of gut microbiota composition has important consequences for human immunodeficiency studies.

Dataset Information

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

Publications

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

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