Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet

Study information

Needs review

study design

time series / longitudinal observational

Citation

PMID PubMed identifier for scientific articles.

30007242

DOI Digital object identifier for electronic documents.

10.1016/j.eplepsyres.2018.06.015

URI

Authors

Zhang Y, Zhou S, Zhou Y, Yu L, Zhang L, Wang Y

Journal

Epilepsy research

Year

2018

Keywords:

Children, Gut microbiota, Ketogenic diet, Refractory epilepsy

OBJECTIVE: The aim of this study was to investigate the characteristics and composition of intestinal microbiota in children with refractory epilepsy after ketogenic diet (KD) therapy and to explore the bacterial biomarkers related to clinical efficacy. METHODS: We prospectively analyzed 20 patients (14 males, 6 females) treated with KD. Clinical efficacy, electroencephalogram (EEG) changes, and laboratory tests were evaluated, and fecal specimens were obtained prior to and 6 months after therapy. The composition of gut microbiota was analyzed by 16S rDNA sequencing, and we screened the possible flora associated with efficacy of the KD. RESULTS: After 6 months of treatment, 2 patients were seizure free, 3 had ≥ 90% seizure reduction, 5 had a reduction of 50-89%, and 10 had < 50% reduction. All 10 responders showed an improvement in EEG. Compared with baseline, fecal microbial profiles showed lower alpha diversity after KD therapy and revealed significantly decreased abundance of Firmicutes and increased levels of Bacteroidetes. We also observed that Clostridiales, Ruminococcaceae, Rikenellaceae, Lachnospiraceae, and Alistipes were enriched in the non-responsive group. CONCLUSIONS: The results show that the KD can reduce the species richness and diversity of intestinal microbiota. The changes of gut microbiota may be associated with different efficacy after KD, and specific gut microbiota may serve as an efficacy biomarker and a potential therapeutic target in patients with refractory epilepsy.

Experiment 1

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Curated date: 2024/11/20

Curator: Kavyaayala

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Subjects

Location of subjects: China

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,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),Epilepsy

Group 0 name Corresponds to the control (unexposed) group for case-control studies: pre-treatment group

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

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Group treated for 6 months with ketogenic diet therapy. Had to have intractable epilepsy defined as 2 or more drugs used without achieving control, and required to have no secondary etiologies before treatment began. All of the patients were instructed to a non-fasting diet with a classic 4:1 ratio KD (fat:protein plus carbohydrate). A percentage (75–100%) of the recommended daily allowance of energy was used, and it was adjusted based on the evaluation of growth. Fat from pork, oils such as olive oil, coconut oil, and other sources was a critical part of the diet. Plant fat accounted for about 70% of the amount of fat. The diet composition included at least 1 g of protein per kg body weight from animal sources (e.g. eggs, meat, poultry and fish). Carbohydrate-containing foods such as fruits and vegetables were added.

Group 0 sample size Number of subjects in the control (unexposed) group: 20

Group 1 sample size Number of subjects in the case (exposed) group: 20

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): excluded from study if antibiotics taken within two weeks of initial fecal sampling

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

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

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

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

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Chao1 Abundance-based estimator of species richness: unchanged

Simpson Estimator of species richness and species evenness: more weight on species evenness: unchanged

Signature 1

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Curated date: 2024/11/20

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Source: Figure 2

Description: Comparing difference in intestinal microbiome of KD treated children after treatment implementation vs before treatment

Abundance in Group 1: increased abundance in treatment group

NCBI	Quality Control	Links
Bacteroidaceae
Bacteroidales
Bacteroides
Bacteroidia
Bacteroidota

Revision editor(s): Kavyaayala

Signature 2

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incomplete

Curated date: 2024/11/20

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 2

Description: Comparing difference in intestinal microbiome of KD treated children after treatment implementation vs before treatment

Abundance in Group 1: decreased abundance in treatment group

NCBI	Quality Control	Links
Acinetobacter
Actinomycetales
Actinomycetes
Actinomycetota
Bacillota
Burkholderiaceae
Clostridia
Coprobacter
Faecalibacterium
Lachnospiraceae incertae sedis
Leucobacter
Microbacteriaceae
Moraxellaceae
Pseudomonadaceae
Pseudomonadales
Pseudomonas

Revision editor(s): Kavyaayala