Higher levels of Bifidobacteria and tumor necrosis factor in children with drug-resistant epilepsy are associated with anti-seizure response to the ketogenic diet
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Dahlin M, Singleton SS, David JA, Basuchoudhary A, Wickström R, Mazumder R, Prast-Nielsen S
Journal
EBioMedicine
Year
2022
Keywords:
Bifidobacterium, Bioinformatics, Epilepsy, Gut microbiota, Inflammation, Ketogenic diet, Machine learning, Omics, TNF
BACKGROUND: Recently, studies have suggested a role for the gut microbiota in epilepsy. Gut microbial changes during ketogenic diet (KD) treatment of drug-resistant epilepsy have been described. Inflammation is associated with certain types of epilepsy and specific inflammation markers decrease during KD. The gut microbiota plays an important role in the regulation of the immune system and inflammation. METHODS: 28 children with drug-resistant epilepsy treated with the ketogenic diet were followed in this observational study. Fecal and serum samples were collected at baseline and three months after dietary intervention. FINDINGS: We identified both gut microbial and inflammatory changes during treatment. KD had a general anti-inflammatory effect. Novel bioinformatics and machine learning approaches identified signatures of specific Bifidobacteria and TNF (tumor necrosis factor) associated with responders before starting KD. During KD, taxonomic and inflammatory profiles between responders and non-responders were more similar than at baseline. INTERPRETATION: Our results suggest that children with drug-resistant epilepsy are more likely to benefit from KD treatment when specific Bifidobacteria and TNF are elevated. We here present a novel signature of interaction of the gut microbiota and the immune system associated with anti-epileptic response to KD treatment. This signature could be used as a prognostic biomarker to identify potential responders to KD before starting treatment. Our findings may also contribute to the development of new anti-seizure therapies by targeting specific components of the gut microbiota. FUNDING: This study was supported by the Swedish Brain Foundation, Margarethahemmet Society, Stiftelsen Sunnerdahls Handikappfond, Linnea & Josef Carlssons Foundation, and The McCormick Genomic & Proteomic Center.
Experiment 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
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,feces
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Response to ketogenic diet Response to ketogenic diet,response to ketogenic diet
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Responders before ketogenic diet (R_Ep1)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders during ketogenic diet (R_Ep2)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group consists of children with ≥50% seizure reduction during ketogenic diet treatment.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 27
- Group 1 sample size Number of subjects in the case (exposed) group
- 27
- 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
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- centered log-ratio
- Statistical test
- Welch's T-Test
- 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
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Source: Figure 4C
Description: Fecal microbiome of R_Ep2 group compared to R_Ep1 group
Abundance in Group 1: decreased abundance in Responders during ketogenic diet (R_Ep2)
Revision editor(s): Kavyaayala, WikiWorks
Experiment 2
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Decreasing correlation in non-responders before ketogenic diet (NR_Ep1)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Increasing correlation in non-responders before ketogenic diet (NR_Ep1)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group consists of children with a < 50% reduction before ketogenic diet treatment.
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Source: Figure 4B
Description: Spearman's correlation of members of the B. longum cluster.
Abundance in Group 1: decreased abundance in Increasing correlation in non-responders before ketogenic diet (NR_Ep1)
Revision editor(s): Victoria
Experiment 3
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Decreasing correlation in non-responders during ketogenic diet (NR_Ep2)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Increasing correlation in non-responders during ketogenic diet (NR_Ep2)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group consists of children with a <50% seizure reduction during ketogenic diet treatment.
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Source: Figure 4B
Description: Spearman's correlation of members of the B. longum cluster.
Abundance in Group 1: decreased abundance in Increasing correlation in non-responders during ketogenic diet (NR_Ep2)
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium longum subsp. infantis |
Revision editor(s): Victoria
Experiment 4
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders before ketogenic diet (NR_Ep1)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders before ketogenic diet (R_Ep1)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group consists of children with ≥50% seizure reduction before ketogenic diet treatment.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 27
- Group 1 sample size Number of subjects in the case (exposed) group
- 27
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Source: Figure 4C
Description: Fecal microbiome of R_Ep1 group compared to NR_Ep1 group
Abundance in Group 1: increased abundance in Responders before ketogenic diet (R_Ep1)
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium breve JCM 7019 | ||
| Bifidobacterium longum DJO10A | ||
| Bifidobacterium longum subsp. infantis | ||
| Bifidobacterium longum subsp. infantis ATCC 15697 = JCM 1222 = DSM 20088 |
Revision editor(s): Kavyaayala, WikiWorks
Experiment 5
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Decreasing correlation in responders during ketogenic diet (R_Ep2)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Increasing correlation in responders during ketogenic diet (R_Ep2)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- This group consists of children with a ≥50% seizure reduction during ketogenic diet treatment.
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Signature 1
Reviewed Marked as Reviewed by KateRasheed on 2025-6-11
Source: Figure 4B
Description: Spearman's correlation of members of the B. longum cluster.
Abundance in Group 1: decreased abundance in Increasing correlation in responders during ketogenic diet (R_Ep2)
| NCBI | Quality Control | Links |
|---|---|---|
| Bifidobacterium longum subsp. infantis | ||
| Bifidobacterium longum subsp. longum JDM301 |
Revision editor(s): Victoria
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