Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet
Abstract
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.
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Fecal microbial profiles showed lower alpha diversity, decreased abundance of Firmicutes, and increased levels of Bacteroidetes after ketogenic diet.
“Fecal microbial profiles showed lower alpha diversity, decreased abundance of Firmicutes and increased levels of Bacteroidetes after ketogenic diet.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [364]
In another study of 20 children with drug-resistant epilepsy, after 6 months of ketogenic diet 2 patients were seizure free, 3 had ≥90% seizure reduction, 5 had 50-89% reduction, and 10 had <50% reduction.
“In another study 20 children with drug-resistant epilepsy were enrolled.After 6 months of the ketogenic diet 2 patients were seizure free, 3 had ≥ 90% seizure reduction, 5 had a reduction of 50-89%, and 10 had < 50% reduction.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [364]
Enrichment in Clostridiales, Ruminococcaceae, Rikenellaceae, Lachnospiraceae, and Alistipes was observed in the non-responsive group.
“Furthermore, enrichment in Clostridiales, Ruminococcaceae, Rikenellaceae, Lachnospiraceae, and Alistipes was observed in the non-responsive group [364].”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [364]
Cites
UPARSE: highly accurate OTU sequences from microbial amplicon reads
Edgar, R. C. (2013) · Nature Methods · doi:10.1038/nmeth.2604 · Cited by 16,587 · see citing works
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100 · see citing works
The impact of the gut microbiota on human health: an integrative view
Clemente, J. C., Ursell, L. K., Parfrey, L. W., & Knight, R. (2012) · Cell · doi:10.1016/j.cell.2012.01.035 · Cited by 3,710 · see citing works
Host microbiota constantly control maturation and function of microglia in the CNS
Erny, D., Hrabě de Angelis, A. L., Jaitin, D., Wieghofer, P., Staszewski, O., David, E., Keren-Shaul, H., Mahlakoiv, T., Jakobshagen, K., Buch, T., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4030 · Cited by 3,569 · see citing works
Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life
Bäckhed, F., Roswall, J., Peng, Y., Feng, Q., Jia, H., Kovatcheva-Datchary, P., Li, Y., Xia, Y., Xie, H., Zhong, H., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.004 · Cited by 3,315 · see citing works
Kelly, J. R., Borre, Y., O' Brien, C., Patterson, E., El Aidy, S., Deane, J., Kennedy, P. J., Beers, S., Scott, K., Moloney, G., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.07.019 · Cited by 1,683 · see citing works
The central nervous system and the gut microbiome
Sharon, G., Sampson, T. R., Geschwind, D. H., & Mazmanian, S. K. (2016) · Cell · doi:10.1016/j.cell.2016.10.027 · Cited by 1,513 · see citing works
The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial
Neal, E. G., Chaffe, H., Schwartz, R. H., Lawson, M. S., Edwards, N., Fitzsimmons, G., Whitney, A., & Cross, J. H. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70092-9 · Cited by 1,227 · see citing works
Unger, M. M., Spiegel, J., Dillmann, K.-U., Grundmann, D., Philippeit, H., Bürmann, J., Faßbender, K., Schwiertz, A., & Schäfer, K.-H. (2016) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2016.08.019 · Cited by 1,159 · see citing works
Correlation between the human fecal microbiota and depression
Naseribafrouei, A., Hestad, K., Avershina, E., Sekelja, M., Linløkken, A., Wilson, R., & Rudi, K. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12378 · Cited by 1,044 · see citing works
Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls
Chen, J., Chia, N., Kalari, K. R., Yao, J. Z., Novotna, M., Paz Soldan, M. M., Luckey, D. H., Marietta, E. V., Jeraldo, P. R., Chen, X., et al. (2016) · Scientific Reports · doi:10.1038/srep28484 · Cited by 933 · see citing works
Meehan, C. J., & Beiko, R. G. (2014) · Genome Biology and Evolution · doi:10.1093/gbe/evu050 · Cited by 708 · see citing works
The structure and diversity of human, animal and environmental resistomes
Pal, C., Bengtsson‐Palme, J., Kristiansson, E., & Larsson, D. G. J. (2016) · Microbiome · doi:10.1186/s40168-016-0199-5 · Cited by 508 · see citing works
The Epidemiology of Global Epilepsy
Singh, A., & Trevick, S. A. (2016) · Neurologic Clinics · doi:10.1016/j.ncl.2016.06.015 · Cited by 423 · see citing works
Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer’s Mouse Model
Brandscheid, C., Schuck, F., Reinhardt, S., Schäfer, K.-H., Pietrzik, C. U., Grimm, M., Hartmann, T., Schwiertz, A., & Endres, K. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160926 · Cited by 318 · see citing works
Xie, G., Zhou, Q., Qiu, C.-Z., Dai, W.-K., Wang, H.-P., Li, Y.-H., Liao, J.-X., Lu, X.-G., Lin, S.-F., Ye, J.-H., et al. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i33.6164 · Cited by 291 · see citing works
Ketogenic diet modifies the gut microbiota in a murine model of autism spectrum disorder
Newell, C., Bomhof, M. R., Reimer, R. A., Hittel, D. S., Rho, J. M., & Shearer, J. (2016) · Molecular Autism · doi:10.1186/s13229-016-0099-3 · Cited by 272 · see citing works
Gut microbiota and autism: key concepts and findings
Ding, H. T., Taur, Y., & Walkup, J. T. (2017) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-016-2960-9 · Cited by 232 · see citing works
The tantalizing links between gut microbes and the brain
Smith, P. A. (2015) · Nature · doi:10.1038/526312a · Cited by 221 · see citing works
Schmidt, C. (2015) · Nature · doi:10.1038/518s13a · Cited by 158 · see citing works
Altered gut microbiota in Rett syndrome
Strati, F., Cavalieri, D., Albanese, D., Felice, C. D., Donati, C., Hayek, J., Jousson, O., Leoncini, S., Pindo, M., Renzi, D., et al. (2016) · Microbiome · doi:10.1186/s40168-016-0185-y · Cited by 148 · see citing works
The human gut microbiome, a taxonomic conundrum
Sankar, S. A., Lagier, J., Pontarotti, P., Raoult, D., & Fournier, P. (2015) · Systematic and Applied Microbiology · doi:10.1016/j.syapm.2015.03.004 · Cited by 144 · see citing works
Wang, L., Zeng, B., Liu, Z., Liao, Z., Zhong, Q., Gu, L., Wei, H., & Fang, X. (2018) · Journal of Food Science · doi:10.1111/1750-3841.14058 · Cited by 137 · see citing works
Tagliabue, A., Ferraris, C., Uggeri, F., Trentani, C., Bertoli, S., de Giorgis, V., Veggiotti, P., & Elli, M. (2017) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2016.11.003 · Cited by 126 · see citing works
Altered Fecal Microbiota in Paediatric Inflammatory Bowel Disease
Maukonen, J., Kolho, K., Paasela, M., Honkanen, J. K., Klemetti, P., Vaarala, O., & Saarela, M. (2015) · Journal of Crohn s and Colitis · doi:10.1093/ecco-jcc/jjv147 · Cited by 106 · see citing works
The ketogenic diet in pharmacoresistant childhood epilepsy
Winesett, S. P., Bessone, S. K., & Kossoff, E. H. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1044982 · Cited by 78 · see citing works
Hedin, C. R. H., Gast, C., Stagg, A. J., Lindsay, J. O., & Whelan, K. (2017) · Gut Microbes · doi:10.1080/19490976.2017.1284733 · Cited by 45 · see citing works
The Elusive Compass of Clostridial Neurotoxins: Deciding When and Where to Go?
Bercsényi, K., Giribaldi, F., & Schiavo, G. (2012) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-33570-9_5 · Cited by 40 · see citing works
Diversity of Gut Microbiota Metabolic Pathways in 10 Pairs of Chinese Infant Twins
Zhou, S., Xu, R., He, F., Zhou, J., Wang, Y., Zhou, J., Wang, M., & Zhou, W. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161627 · Cited by 38 · see citing works
Self-citationTherapeutic effects of the ketogenic diet in children with Lennox-Gastaut syndrome
Zhang, Y., Wang, Y., Zhou, Y., et al. (2016) · Epilepsy Research · doi:10.1016/j.eplepsyres.2016.11.003 · Cited by 32 · see citing works
Self-citationFinnie, J. W., Manavis, J., & Chidlow, G. (2014) · Journal of Comparative Pathology · doi:10.1016/j.jcpa.2014.04.010 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The gut microbiota at the intersection of diet and human health
Gentile, C. L., & Weir, T. L. (2018) · Science · doi:10.1126/science.aau5812 · Cited by 1,049 · see citing works
The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders
Socała, K., Doboszewska, U., Szopa, A., Serefko, A., Włodarczyk, M., Zielińska, A., Poleszak, E., Fichna, J., & Wlaź, P. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105840 · Cited by 857 · see citing works
Lindefeldt, M., Eng, A., Darban, H., Bjerkner, A., Zetterström, C. K., Allander, T., Andersson, B., Borenstein, E., Dahlin, M., & Prast-Nielsen, S. (2019) · npj Biofilms and Microbiomes · doi:10.1038/s41522-018-0073-2 · Cited by 310 · see citing works
Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders
Horn, J., Mayer, D. E., Chen, S., & Mayer, E. A. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01922-0 · Cited by 193 · see citing works
Microbiota-gut brain axis involvement in neuropsychiatric disorders
Iannone, L. F., Preda, A., Blottière, H. M., Clarke, G., Albani, D., Belcastro, V., Carotenuto, M., Cattaneo, A., Citraro, R., Ferraris, C., et al. (2019) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2019.1638763 · Cited by 177 · see citing works
Spichak, S., Bastiaanssen, T. F. S., Berding, K., Vlckova, K., Clarke, G., Dinan, T. G., & Cryan, J. F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.044 · Cited by 127 · see citing works
Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis
Sourbron, J., Klinkenberg, S., van Kuijk, S. M. J., Lagae, L., Lambrechts, D., Braakman, H. M. H., & Majoie, M. (2020) · Child's Nervous System · doi:10.1007/s00381-020-04578-7 · Cited by 111 · see citing works
Can we ‘seize’ the gut microbiota to treat epilepsy?
De Caro, C., Iannone, L. F., Citraro, R., Striano, P., De Sarro, G., Constanti, A., Cryan, J. F., & Russo, E. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.10.002 · Cited by 110 · see citing works
Reddel, S., Putignani, L., & Del Chierico, F. (2019) · Nutrients · doi:10.3390/nu11020373 · Cited by 104 · see citing works
Gut bacterial dysbiosis in children with intractable epilepsy
Lee, K., Kim, N., Shim, J. O., & Kim, G.-H. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm10010005 · Cited by 70 · see citing works
Gut microbiota and epilepsy: a systematic review on their relationship and possible therapeutics
Arulsamy, A., Tan, Q. Y., Balasubramaniam, V., O’Brien, T. J., & Shaikh, M. F. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00431 · Cited by 65 · see citing works
Dietary Regulation of Gut-Brain Axis in Alzheimer’s Disease: Importance of Microbiota Metabolites
Frausto, D. M., Forsyth, C. B., Keshavarzian, A., & Voigt, R. M. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.736814 · Cited by 61 · see citing works
Lee, H., Lee, S., Lee, D.-H., & Kim, D. W. (2021) · Epilepsy Research · doi:10.1016/j.eplepsyres.2021.106601 · Cited by 57 · see citing works
- Authors
- Zhang, Y., Zhou, S., Zhou, Y., Yu, L., Zhang, L., & Wang, Y.
- Affiliations
- Children's Hospital of Fudan University (CN)
- Corresponding author
- Wang, Yi
- Venue
- Epilepsy Research
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 145
- Pages
- 163-168
- ISSN
- 0920-1211 (ISSN-L)
- OpenAlex
- W2809960745
- Cited by
- 269
- References
- 31
- Citations by year
- 2026: 19 · 2025: 34 · 2024: 31 · 2023: 41 · 2022: 56 · 2021: 37 · 2020: 23 · 2019: 24 · 2018: 3
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epilepsy Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Research Project of Shanghai Municipal Commission of Health and Family Planning (201640065)
- Key Research Project of the Ministry of Science and Technology of China (2016YFC0904400)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Keywords
- gut microbiota, drug-resistant epilepsy, ketogenic diet, children, bacterial biomarkers, treatment response, alpha diversity, Firmicutes, Bacteroidetes, Clostridiales, Ruminococcaceae, Lachnospiraceae, Alistipes, EEG improvement, seizure reduction
- MeSH terms
- Gastrointestinal Microbiome, Drug Resistant Epilepsy, Child, Child, Preschool, Electroencephalography, Female, Humans, Infant, Male, Retrospective Studies, RNA, Ribosomal, 16S, Diet, Ketogenic
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