Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Xie G, Zhou Q, Qiu CZ, Dai WK, Wang HP, Li YH, Liao JX, Lu XG, Lin SF, Ye JH, Ma ZY, Wang WJ
Journal
World journal of gastroenterology
Year
2017
Keywords:
Cronobacter, Epilepsy, Gut microbiota, Ketogenic diet, Seizures
AIM: To investigate whether patients with refractory epilepsy and healthy infants differ in gut microbiota (GM), and how ketogenic diet (KD) alters GM. METHODS: A total of 14 epileptic and 30 healthy infants were recruited and seizure frequencies were recorded. Stool samples were collected for 16S rDNA sequencing using the Illumina Miseq platform. The composition of GM in each sample was analyzed with MOTHUR, and inter-group comparison was conducted by R software. RESULTS: After being on KD treatment for a week, 64% of epileptic infants showed an obvious improvement, with a 50% decrease in seizure frequency. GM structure in epileptic infants (P1 group) differed dramatically from that in healthy infants (Health group). Proteobacteria, which had accumulated significantly in the P1 group, decreased dramatically after KD treatment (P2 group). Cronobacter predominated in the P1 group and remained at a low level both in the Health and P2 groups. Bacteroides increased significantly in the P2 group, in which Prevotella and Bifidobacterium also grew in numbers and kept increasing. CONCLUSION: GM pattern in healthy infants differed dramatically from that of the epileptic group. KD could significantly modify symptoms of epilepsy and reshape the GM of epileptic infants.

Experiment 1


Needs review

Curated date: 2024/10/10

Curator: Kavyaayala

Revision editor(s): Kavyaayala

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
healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
epileptic infants after treatment (P2)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Convulsion more than four times per week after treatment with ≥ 3 AEDs; no antibiotic exposure for at least 1 mo; no known genetic metabolic disorders or severe systemic illnesses; and successive KD therapy for at least 1 wk. KD was provided by Zeneca (Shenzhen, China), including Qitong ketogenic liquid milk (3.4 g protein, 8.0 g lipid and 0.6 g carbohydrate per 100 g milk), Qitong ketogenic cookies and Qitong ketogenic set-meal packages
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
14
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
1 month

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
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
Matched on Factors on which subjects have been matched on in a case-control study
age


Signature 1

Needs review

Curated date: 2024/11/14

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Supplementary Table 5

Description: Difference between the fecal microbiome of patients with refractory epilepsy after KD treatment (P2) vs healthy controls

Abundance in Group 1: increased abundance in epileptic infants after treatment (P2)

NCBI Quality ControlLinks
Acinetobacter
Bacillus
Butyricicoccus
Cronobacter
Eggerthella
Enterococcus
Erysipelatoclostridium sp. An173
Gemella
Klebsiella
Lactococcus
Lactonifactor
Odoribacter
Peptoclostridium
Pseudomonas
Ruminiclostridium

Revision editor(s): Kavyaayala

Signature 2

Needs review

Curated date: 2024/11/15

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Supplementary Table 5

Description: Difference between the fecal microbiome of patients with refractory epilepsy after KD treatment (P2) vs healthy controls

Abundance in Group 1: decreased abundance in epileptic infants after treatment (P2)

NCBI Quality ControlLinks
Actinomyces
Bifidobacterium
Bilophila
Clostridium
Escherichia
Faecalibacterium
Granulicatella
Haemophilus
Lachnoclostridium

Revision editor(s): Kavyaayala

Experiment 2


Needs review

Curated date: 2024/11/15

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
epileptic infants before treatment (P1)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Convulsion more than four times per week after treatment with ≥ 3 AEDs; no antibiotic exposure for at least 1 mo; no known genetic metabolic disorders or severe systemic illnesses

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/16

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Supplementary Table 5

Description: Difference between the fecal microbiome of patients with refractory epilepsy before KD treatment (P1) vs healthy controls

Abundance in Group 1: increased abundance in epileptic infants before treatment (P1)

NCBI Quality ControlLinks
Acinetobacter
Bacillus
Butyricicoccus
Cronobacter
Dysgonomonas
Eggerthella
Enterococcus
Erysipelatoclostridium sp. An173
Gemella
Klebsiella
Lactococcus
Lactonifactor
Mogibacterium
Odoribacter
Peptoclostridium
Porphyromonas
Pseudomonas
Psychrobacter
Ralstonia
Streptococcus

Revision editor(s): Kavyaayala

Signature 2

Needs review

Curated date: 2024/11/16

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Supplementary Table 5

Description: Difference between the fecal microbiome of patients with refractory epilepsy before KD treatment (P1) vs healthy controls

Abundance in Group 1: decreased abundance in epileptic infants before treatment (P1)

NCBI Quality ControlLinks
Actinomyces
Atopobium
Bacteroides
Bifidobacterium
Bilophila
Clostridium
Escherichia
Granulicatella
Haemophilus

Revision editor(s): Kavyaayala

Experiment 3


Needs review

Curated date: 2024/11/15

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
both healthy controls and epileptic infants before treatment (P1)
Group 1 name Corresponds to the case (exposed) group for case-control studies
epileptic infants after treatment (P2)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Convulsion more than four times per week after treatment with ≥ 3 AEDs; no antibiotic exposure for at least 1 mo; no known genetic metabolic disorders or severe systemic illnesses; and successive KD therapy for at least 1 wk. KD was provided by Zeneca (Shenzhen, China), including Qitong ketogenic liquid milk (3.4 g protein, 8.0 g lipid and 0.6 g carbohydrate per 100 g milk), Qitong ketogenic cookies and Qitong ketogenic set-meal packages
Group 0 sample size Number of subjects in the control (unexposed) group
44

Lab analysis

Statistical Analysis

Statistical test
LEfSe
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2


Signature 1

Needs review

Curated date: 2024/11/16

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 4

Description: Difference between the fecal microbiome of patients with refractory epilepsy after KD treatment (P2) vs epileptic infants before treatment (P1) and healthy controls

Abundance in Group 1: increased abundance in epileptic infants after treatment (P2)

NCBI Quality ControlLinks
Bacillaceae
Bacillales
Bacillus
Brochothrix
Eggerthella
Eggerthellaceae
Eggerthellales
Listeriaceae
Odoribacter
Parvimonas
Peptoclostridium
Solobacterium

Revision editor(s): Kavyaayala

Experiment 4


Needs review

Curated date: 2024/11/16

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
both healthy controls and epileptic infants after treatment (P2)
Group 1 name Corresponds to the case (exposed) group for case-control studies
epileptic infants before treatment (P1)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Convulsion more than four times per week after treatment with ≥ 3 AEDs; no antibiotic exposure for at least 1 mo; no known genetic metabolic disorders or severe systemic illnesses

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2024/11/17

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 4

Description: Difference between the fecal microbiome of patients with refractory epilepsy after KD treatment (P2) vs epileptic infants before treatment (P1) and healthy controls

Abundance in Group 1: increased abundance in epileptic infants before treatment (P1)

NCBI Quality ControlLinks
Acinetobacter
Bacilli
Butyricicoccus
Clostridiaceae
Cronobacter
Enterobacterales
Enterobacteriaceae
Enterococcaceae
Enterococcus
Erysipelatoclostridium sp. An173
Erysipelotrichaceae
Erysipelotrichales
Erysipelotrichia
Gammaproteobacteria
Hungatella
Klebsiella
Lachnoclostridium
Lactobacillales
Lactococcus
Leuconostocaceae bacterium
Mogibacterium
Myroides
Peptoniphilus
Peptostreptococcus
Psychrobacter
Ruminiclostridium
Sphingomonadaceae
Streptococcaceae
Streptococcus
Weissella
unclassified Clostridiales Family XIII

Revision editor(s): Kavyaayala

Experiment 5


Needs review

Curated date: 2024/11/16

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
combined data from epileptic infants both before (P1) and after treatment (P2)
Group 1 name Corresponds to the case (exposed) group for case-control studies
healthy controls
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
No antibiotic exposure for at least 1 mo before this study, no disease symptoms for at least 1 mo following recruitment, and no history of seizures
Group 0 sample size Number of subjects in the control (unexposed) group
28
Group 1 sample size Number of subjects in the case (exposed) group
30

Lab analysis

Statistical Analysis

Matched on Factors on which subjects have been matched on in a case-control study
Not specified


Signature 1

Needs review

Curated date: 2024/11/17

Curator: Kavyaayala

Revision editor(s): Kavyaayala

Source: Figure 4

Description: Difference between the fecal microbiome of healthy controls vs patients with refractory epilepsy both before (P1) and after treatment (P2)

Abundance in Group 1: increased abundance in healthy controls

NCBI Quality ControlLinks
Actinomyces
Actinomycetaceae
Actinomycetales
Actinomycetes
Actinomycetota
Bacteroidaceae
Bacteroides
Betaproteobacteria
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Burkholderiales
Campylobacter
Campylobacteraceae
Campylobacterales
Candidatus Saccharibacteria
Clostridium
Epsilonproteobacteria
Escherichia
Faecalibacterium
Haemophilus
Pasteurellaceae
Pasteurellales
Ruminococcus
Staphylococcaceae
Staphylococcus
Sutterella
Sutterellaceae

Revision editor(s): Kavyaayala