4.3 Article

Investigation of the association between imbalance of the intestinal flora and infantile spasms: a pilot case-control study

Journal

TRANSLATIONAL PEDIATRICS
Volume 10, Issue 4, Pages 819-833

Publisher

AME PUBL CO
DOI: 10.21037/tp-20-384

Keywords

Infantile spasm (IS); gastrointestinal microbiome; adrenocorticotropic hormone; treatment

Categories

Funding

  1. National Natural Science Foundation of China [81671279]
  2. Medical Big Data and Artificial Intelligence Research and Development Project of Chinese PLA General Hospital [2019MBD-004]

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The study revealed a specific relationship between the intestinal flora and infantile spasms, showing that the imbalance of the intestinal flora may be involved in the pathogenesis of infantile spasms and is related to response to ACTH treatment. Regulating the composition of the intestinal flora could potentially serve as an adjuvant therapy for patients with infantile spasms.
Background: The intestinal flora (IF) regulates brain function via the neuroendocrine and neuroimmune systems and influences the development of several neuropsychiatric diseases, including epilepsy. Here, we investigated the specific relationship between the IF and infantile spasms (IS), a specific form of epilepsy. Methods: Twenty-three children suffering from IS were recruited from the Chinese PLA General Hospital. According to patient response to adrenocorticotropic hormone (ACTH) treatment, the cohort was subdivided into 2 groups: an ACTH-response group and an ACTH-no response (NR) group. A total of 21 healthy children were recruited as a control group (healthy controls: HCs) during the same time period. Fecal samples were collected from infants in the IS and HC groups, and the population of fecal microorganisms was analyzed by 16s ribosomal DNA sequencing. The alpha and beta diversity of the fecal microflora was determined, and the relative abundance of each species was classified. Tax4Fun2 was used to analyze the metabolic pathways utilized by the microflora, and the Kyoto Encyclopedia of Genes and Genomes database was used to analyze differentially expressed genes and pathways. Results: No significant differences existed in alpha or beta diversity when compared between the IS and HC groups, nor between the ACTH-response and ACTH-NR groups which were separated before and after ACTH treatment. Although there was no significant difference between the ACTH-response and ACTHNR groups with respect to a diversity, there was a significant difference in beta diversity. Compared with that of the HCs, the IF of the IS group featured lower proportions of Lactobacillus, Roseburia, and Lachnospira, and a higher proportion of Clostridium. In the IS group, the proportion of Staphylococcus in the IF was higher before treatment than after treatment. Compared with the ACTH-NR group, the ACTH-response group had reduced populations of Odoribacter, Phascolarctobacterium, Anaerotruncus, Mitsuakella, and Robinsoniella. However, an increase was observed in the population of Bifidobacterium. A significant difference was also identified between the IS and HC groups with regard to the expression levels of genes associated with lipoic acid synthesis. Conclusions: Our analysis demonstrated that imbalance of the IF may be involved in the pathogenesis of IS and is related to response to ACTH. Regulating the composition of the IF may pave the way to developing a potential adjuvant therapy for patients with IS.

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