关键词: 生酮饮食, 婴儿痉挛症, 肠道菌群, 宏基因组, 代谢组

Abstract: Objective    To study the changes of gastrointestinal microbiota（GM）and metabolome after receiving ketogenic diet（KD）and explore the microecological etiology of children with infantile spasms（IS）. Methods    We selected sixteen children with IS，who were diagnosed in the Department of Neurology，Shenzhen Children's Hospital between July 2015 and April 2020，aged 6 months to 3 years old.Healthy children（n=30）were enrolled as controls.We collected stool samples from patients at 2 time points，including before KD treatment and 1-week after KD treatment，and fecal samples from healthy children were also collected.The microbial composition and metabolite components were detected by metagenomic and metabolome methods to explore the changes of microbiota composition and metabolism after KD treatment. Results    Principal component analysis（PCA）suggests that the GM pattern of IS patients is significantly different from that of healthy children，but it tends to that of healthy children’s along the KD treatment.The dominant genus is Bacteroides，and the proportion in IS children（22.62%）is lower than that in healthy children（38.86%），and the relative abundance of Bacteroides dorei also reduced significantly in IS children［Healthy group：（3.24±7.14），pre-KD group：（0.19±0.40）；P<0.001］.On the other hand，the Escherichia genus was significantly enriched in patients（P<0.001），and the proportion of corresponding species，Escherichia coli，was also significant enriched in patients’GM（Health group：0.31%，pre-KD group：7.41%；P<0.01）. After KD treatment，the statistical analysis at the species level showed that a variety of Bacteroides increased，such as Bacteroides fragilis，Bacteroides thetaiotaomicron，B. vulgatus，and B.dorei，as well as Faecalibacterium prausnitzii，Akkermansia muciniphila. On the other hand，Bifidobacterium longum and Bifidobacterium breve decreased significantly after KD treatment，as well as E. coli.Based on KEGG analysis，we identified significant abundance differences of multiple metabolic pathways of GM among the three groups，especial for carbohydrate metabolism，gene transcription and translation，and nucleic acid metabolism.The analysis of metabolomics demonstrated that various metabolites，such as capric acid and curcumin，which was related to anti-epileptic effect，were significantly enriched after KD treatment.These differentially abundant metabolites are the key compound to the various KEGG pathway，including metabolic pathways（such as galactose metabolism，phenylalanine metabolism，taurine metabolism），ABC transporters，digestion and absorption of carbohydrates and proteins，etc. Conclusion    There are significant differences in the composition of GM between IS patients and healthy children.B.dorei significantly reduced in IS patients’GM，but E.coli significantly enriched.After KD treatment，Bacteroides，F.prausnitzii and other beneficial bacteria increased.Various neurological diseases related metabolites were detected.These findings provide a new insight to the mechanism about how ketogenic diet improves the clinical symptoms of IS patients.

Key words: ketogenic diet, infantile spasms, gastrointestinal microbiota, metagenome, metabolome