Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2017; 23(33): 6164-6171
Published online Sep 7, 2017. doi: 10.3748/wjg.v23.i33.6164
Ketogenic diet poses a significant effect on imbalanced gut microbiota in infants with refractory epilepsy
Gan Xie, Qian Zhou, Chuang-Zhao Qiu, Wen-Kui Dai, He-Ping Wang, Yin-Hu Li, Jian-Xiang Liao, Xin-Guo Lu, Su-Fang Lin, Jing-Hua Ye, Zhuo-Ya Ma, Wen-Jian Wang
Gan Xie, He-Ping Wang, Zhuo-Ya Ma, Wen-Jian Wang, Department of Respiratory Medicine, Shenzhen Children’s Hospital, Shenzhen 518026, Guangdong Province, China
Qian Zhou, Chuang-Zhao Qiu, Wen-Kui Dai, Yin-Hu Li, WeHealthGene Institute, Shenzhen 518129, Guangdong Province, China
Jian-Xiang Liao, Xin-Guo Lu, Su-Fang Lin, Jing-Hua Ye, Department of Pediatric Neurology, Shenzhen Children’s Hospital, Shenzhen 518026, Guangdong Province, China
Author contributions: Dai WK designed the study and Wang WJ managed the project; Zhou Q and Qiu CZ interpreted the data; Xie G and Zhou Q wrote the manuscript; Qiu CZ and Li YH conducted bioinformatics analysis; Wang HP and Ye JH collected sample information; Liao JX, Lu XG, Lin SF and Ma ZY contributed to the study design and patients’ diagnoses; all authors read and approved the final manuscript. Xie G, Zhou Q and Qiu CZ contributed equally to this work.
Supported by the Innovation Fund of Science and Technology Commission of Shenzhen Municipality, China, No. JCYJ20150403100317071.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Shenzhen Children’s Hospital.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: Sequencing data are available from the NCBI Sequence Read Archive (SRA) database (Accession number: SRP100388).
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Wen-Jian Wang, Doctor, Director, Department of Respiratory Medicine, Shenzhen Children’s Hospital, No. 7019, Yitian Road, Shenzhen 518026, China. dhbk2005@163.com
Telephone: +86-755-83936101 Fax: +86-755-83009800
Received: April 24, 2017
Peer-review started: May 4, 2017
First decision: June 5, 2017
Revised: June 9, 2017
Accepted: July 12, 2017
Article in press: July 12, 2017
Published online: September 7, 2017
Processing time: 126 Days and 18.1 Hours
Abstract
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.

Keywords: Ketogenic diet; Cronobacter; Seizures; Gut microbiota; Epilepsy

Core tip: Many infants with epilepsy are refractory to current antiepileptic drugs, and ketogenic diet (KD) could help to moderate seizure frequency as an alternative treatment. A large number of reports have demonstrated that gut microbiota (GM) can affect children’s neurodevelopment. Concurrently, GM could be dramatically affected by diet. KD could rapidly alter GM and alleviate seizure frequency in infants with refractory epilepsy. The GM structure of epileptic infants - comprising large numbers of pathogens, such as Streptococcus - differed from that of healthy controls. After KD therapy, GM of epileptic patients changed significantly, with fewer pathogens and more beneficial bacteria.