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

Study information

Needs review

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

30701077

DOI Digital object identifier for electronic documents.

10.1038/s41522-018-0073-2

URI

Authors

Lindefeldt M, Eng A, Darban H, Bjerkner A, Zetterström CK, Allander T, Andersson B, Borenstein E, Dahlin M, Prast-Nielsen S

Journal

NPJ biofilms and microbiomes

Year

2019

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.

Experiment 1

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Curated date: 2021/01/10

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Subjects

Location of subjects: Sweden

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: epilepsy [X]Other epilepsy,[X]Other epilepsy (disorder),EF - Epileptic fit,EP - Epilepsy,Epilectic attack, NOS,EPILEP NEC W/O INTR EPIL,EPILEP NOS W/O INTR EPIL,epilepsy,Epilepsy (disorder),Epilepsy and recurrent seizures,EPILEPSY NEC W INTR EPIL,Epilepsy NOS,Epilepsy NOS (disorder),EPILEPSY NOS W INTR EPIL,Epilepsy, NOS,Epilepsy, unspecified,Epilepsy, unspecified, with intractable epilepsy,Epilepsy, unspecified, without mention of intractable epilepsy,Epileptic,Epileptic attack,Epileptic attack, NOS,Epileptic convulsions,Epileptic convulsions, NOS,Epileptic disorder,Epileptic disorder, NOS,Epileptic fit,Epileptic fits,Epileptic fits, NOS,Epileptic Seizure,Epileptic seizure (finding),Epileptic seizures,Epileptic seizures, NOS,Generalised convulsion,Generalised fit,Generalised seizure,Generalized convulsion,Generalized fit,Generalized seizure,Generalized seizure (finding),Other forms of epilepsy,Other forms of epilepsy (disorder),Other forms of epilepsy and recurrent seizures,Other forms of epilepsy NOS,Other forms of epilepsy NOS (disorder),Other forms of epilepsy, with intractable epilepsy,Other forms of epilepsy, without mention of intractable epilepsy,Seizure disorder,seizure disorder,Seizure disorder (disorder)

Group 0 name Corresponds to the control (unexposed) group for case-control studies: after keto diet

Group 1 name Corresponds to the case (exposed) group for case-control studies: before keto diet

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: children with therapy resistent inoperabe epilepsy or a diagnosis of a neorometablic disorder in which KD is recommended

Group 0 sample size Number of subjects in the control (unexposed) group: 12

Group 1 sample size Number of subjects in the case (exposed) group: 12

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 3 months

Lab analysis

Sequencing type: WMS

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: Yes

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 4

Signature 1

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Curated date: 2021/01/10

Curator: Fatima Zohra

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Source: Figure 3

Description: Statistical changes at all taxonomic levels during dietary interventaion (keto diet) using LEFse method

Abundance in Group 1: increased abundance in before keto diet

NCBI	Quality Control	Links
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Actinomycetes
Agathobacter rectalis CAG:36
Dialister

Revision editor(s): WikiWorks

Signature 2

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Mark reviewed

Your review change was submitted

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Curated date: 2021/01/10

Curator: Fatima Zohra

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Source: Figure 3

Description: Statistical changes at all taxonomic levels during dietary interventaion (keto diet) using LEFse method

Abundance in Group 1: decreased abundance in before keto diet

NCBI	Quality Control	Links
Escherichia coli
Escherichia
Gammaproteobacteria
Enterobacteriaceae
Enterobacterales
Pseudomonadota

Revision editor(s): WikiWorks