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

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
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


Needs review

Curated date: 2024/11/20

Curator: Kavyaayala

Revision editor(s): Kavyaayala, WikiWorks

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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
pre-ketogenic diet
Group 1 name Corresponds to the case (exposed) group for case-control studies
post-ketogenic diet
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
children with intractable epilepsy after ketogenic diet treatment
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)
two weeks

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
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

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

Needs review

Curated date: 2024/11/20

Curator: Kavyaayala

Revision editor(s): Kavyaayala, WikiWorks

Source: Figure 2

Description: Fecal microbiome of post-ketogenic diet group compared to pre-ketogenic diet group

Abundance in Group 1: increased abundance in post-ketogenic diet

NCBI Quality ControlLinks
Bacteroidaceae
Bacteroidales
Bacteroides
Bacteroidia
Bacteroidota

Revision editor(s): Kavyaayala, WikiWorks

Signature 2

Needs review

Curated date: 2024/11/20

Curator: Kavyaayala

Revision editor(s): Kavyaayala, WikiWorks

Source: Figure 2

Description: Fecal microbiome of post-ketogenic diet group compared to pre-ketogenic diet group

Abundance in Group 1: decreased abundance in post-ketogenic diet

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

Revision editor(s): Kavyaayala, WikiWorks

Experiment 2


Needs review

Curated date: 2024/11/25

Curator: Kavyaayala

Revision editor(s): Kavyaayala, WikiWorks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
post-ketogenic diet responders
Group 1 name Corresponds to the case (exposed) group for case-control studies
post-ketogenic diet nonresponders
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Nonresponders are patients classified as having less than 50% of seizure frequency reduction after ketogenic diet treatment. This particular group refers to the samples taken from nonresponders post-treatment.
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
10

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/25

Curator: Kavyaayala

Revision editor(s): Kavyaayala, WikiWorks

Source: Figure 3

Description: Fecal microbiome of post-ketogenic diet nonresponders compared to post-ketogenic diet responders

Abundance in Group 1: increased abundance in post-ketogenic diet nonresponders

NCBI Quality ControlLinks
Actinomycetes
Actinomycetota
Alistipes
Anaerotruncus
Blautia
Clostridia
Coriobacteriaceae
Coriobacteriales
Dorea
Eggerthella
Eubacteriales
Fusicatenibacter
Gordonibacter
Helicobacter
Helicobacteraceae
Lachnospiraceae
Lachnospiraceae incertae sedis
Oscillibacter
Oscillospiraceae
Rikenellaceae
Streptococcaceae
Streptococcus
Clostridium XIVaClostridium XIVa
Ruminococcus 2Ruminococcus 2

Revision editor(s): Kavyaayala, WikiWorks