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, 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

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

Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Gut microbial diversity of the three groups. Distribution of Shannon index (evenness) is shown. Red, blue, and green represent the Health, P1 and P2 groups, respectively. The gut microbiota (GM) of the healthy infants was more stable than that of the other two groups.
Figure 2
Figure 2
Principal component analysis. Each plot in the principal component analysis (PCA) graph stands for a sample. Red, blue and green colors represent the Health, P1 and P2 groups, respectively.
Figure 3
Figure 3
Gut microbiota structures in the Health, P1 and P2 groups at the genus level. SVG package (version 1.1) was used to produce the paragraph. The size of the circle representing each genus was determined by the relative abundance of the three groups, and the width of line linking the P1, P2 and Health groups indicates the relative abundance of each group.
Figure 4
Figure 4
Significantly enriched gut microbiota components in the Health, P1 and P2 groups. LEfSe analysis was applied to detect the gut microbiota (GM) components in the three groups. Red, green, and blue represent the Health, P1 and P2 groups, respectively. The LDA score was set as ≤ 2. The enrichment degree is proportional to the LDA score.

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