Hu Baifei, Zhu Xuefen, Zheng Junping, Guo Yanlei, Hu Haiming, Zou Xiaojuan, Yao Xiaowei, Liu Zhanli, Liu Hongtao
College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, China.
Department of Neurology, Hangzhou Children's Hospital, Hangzhou, China.
Eur J Neurol. 2023 Nov;30(11):3516-3528. doi: 10.1111/ene.15275. Epub 2022 Feb 19.
Febrile seizures (FS) pose a severe threat to the neurological development of children. Probing the abnormality of host metabolism is essential for the prevention, diagnosis, and treatment of FS.
Based on clinically collected serum and fecal samples, we used nontargeted metabolomics and 16S rDNA sequencing to explore the relationship of serum metabolite levels and gut microbiota community with the occurrence of FS.
Metabolomic analysis revealed abnormalities in multiple metabolic pathways in serum of FS patients, such as tryptophan metabolism and steroid hormone biosynthesis. Intestinal flora analysis indicated that the α-diversity of gut microbiota in FS patients was significantly reduced. In addition, the relative abundance of a variety of bacteria at the phylum level was remarkably changed in patients with FS, including decreased Firmicutes and Verrucomicrobia. Eleven serum metabolites were identified to be biomarker candidates for FS diagnosis. With the help of a panel biomarker strategy combining four biomarkers as a cluster, four bacteria (i.e., Rothia, Coprococcus, Lactobacillus, and Oscillospira) in a defined panel displayed perfect differentiation of subtypes of FS.
Combining metabolomic and intestinal flora analysis revealed specific characteristics of children with FS, and provided new clues for the diagnosis of FS and the classification of seizure types. In summary, these findings may provide new insights into revealing the significance of serum metabolites and gut microbiota in the pathogenesis of FS.
热性惊厥（FS）对儿童神经发育构成严重威胁。探究宿主代谢异常对于FS的预防、诊断及治疗至关重要。
基于临床收集的血清和粪便样本，我们采用非靶向代谢组学和16S rDNA测序来探索血清代谢物水平及肠道微生物群落与FS发生之间的关系。
代谢组学分析揭示了FS患者血清中多种代谢途径的异常，如色氨酸代谢和类固醇激素生物合成。肠道菌群分析表明，FS患者肠道微生物群的α多样性显著降低。此外，FS患者多种细菌在门水平的相对丰度发生了显著变化，包括厚壁菌门和疣微菌门减少。鉴定出11种血清代谢物作为FS诊断的候选生物标志物。借助将四种生物标志物组合为一组的生物标志物策略，特定组合中的四种细菌（即罗氏菌属、粪球菌属、乳杆菌属和颤螺菌属）对FS亚型表现出完美的区分。
代谢组学与肠道菌群分析相结合揭示了FS患儿的特定特征，并为FS的诊断及癫痫发作类型的分类提供了新线索。总之，这些发现可能为揭示血清代谢物和肠道微生物群在FS发病机制中的意义提供新见解。
