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. 2024 Oct 10:15:1442677.
doi: 10.3389/fimmu.2024.1442677. eCollection 2024.

Study on the gut microbiota, HPA, and cytokine levels in infantile spasms

Jiajia You #  1 , Li Liu #  1 , Xiongfeng Pan  2 , Liwen Wu  3 , Lihong Tan  3 , Changci Zhou  1 , Siwei Fang  1 , Zhenghui Xiao  4 , Jun Qiu  2
Affiliations

Study on the gut microbiota, HPA, and cytokine levels in infantile spasms

Jiajia You et al. Front Immunol. .

Abstract

Objective: The mechanisms driving the progression of infantile spasms are not well understood. We aimed to investigate the changes and correlations of the gut microbiota, the hypothalamus-pituitary-adrenal (HPA) axis hormones, and the inflammatory cytokines in children with infantile spasms before and after treatment in order to provide a reference for future pathogenesis research.

Methods: Children with infantile spasms who were admitted to our hospital were recruited into the case group. The case group was divided into the pre-treatment group (group A, n = 14), the 2 weeks after treatment group (group B), and the 1 month after treatment group (group C). On the other hand, healthy children with the same sex ratio as the case group were recruited into the control group (group D, n = 14). Three stool and blood samples were collected before treatment, 2 weeks after treatment, and 1 month after treatment. The serum samples were analyzed using cytometric bead array (CBA), enzyme-linked immunosorbent assay (ELISA), and chemiluminescent immunoassay (CLIA) to measure the levels of HPA axis hormones and inflammatory cytokines. The collected stool samples were sequenced using 16S rDNA.

Results: The pre-treatment group demonstrated elevated levels of corticotropin-releasing hormone (CRH), interleukin 2 (IL-2), IL-4, IL-6, and IL-17α, which decreased with treatment. The level of CRH was lower in the effective group than that in the ineffective group. Sutterellaceae was lower in the pre-treatment group than that in the control group. Lachnospiracea_incertae_sedis was positively associated with CRH concentration (p < 0.05). After treatment, Sutterellaceae was negatively associated with IL-2 and TNF-α (p < 0.05).

Conclusion: This study found that imbalance of the gut microbiota may be involved in the pathogenesis of infantile spasms and is related to the response to adrenocorticotropic hormone (ACTH). Lachnospiraceae and Lachnospiracea_incertae_sedis might be involved in the disease onset. Sutterellaceae might have a link to children's improved health.

Keywords: HPA axis hormones; correlations; gut microbiota; infantile spasm; inflammatory cytokines.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Comparison of the gut microbiota between the pre-treatment group (group A) and the control group (group D). (A, B) Comparison of the alpha diversity (A) and the beta diversity (B) between the two groups. (C, D) Linear discriminant analysis (LDA) value distribution and the cladogram of the linear discriminant analysis effect size (LEfSe) between the two groups. (E–G) Metastats analysis at the phylum (E), family (F), and genus (G) levels between the two groups.
Figure 2
Figure 2
Comparison of the gut microbiota among the pre-treatment (group A), 2 weeks after treatment (group B), and 1 month after treatment (group C) groups in the case group. (A, B) Comparison of the alpha diversity (A) and the beta diversity (B) among the three groups. (C, D) Linear discriminant analysis (LDA) value distribution and the cladogram of the linear discriminant analysis effect size (LEfSe) among the three groups. (E, F) Metastats analysis at the phylum (E) and family (F) levels among the three groups.
Figure 3
Figure 3
Metastats analysis at the genus level among the pre-treatment group (group A), the 2 weeks after treatment group (group B), and the 1 month after treatment group (group C) in the case group.
Figure 4
Figure 4
Comparison of the gut microbiota between the effective (BE) and ineffective (BNE) groups in the 2 weeks after treatment group. (A, B) Comparison of the alpha diversity (A) and the beta diversity (B) between the two groups. (C, D) Linear discriminant analysis (LDA) value distribution and the cladogram of the linear discriminant analysis effect size (LEfSe) between the two groups. (E–G) Metastats analysis at the phylum (E), family (F), and genus (G) levels between the two groups.
Figure 5
Figure 5
Correlation analysis between the gut microbiota and the levels of hypothalamus–pituitary–adrenal (HPA) axis hormones and inflammatory cytokines. (A) Correlation analysis of the pre-treatment (group A), 2 weeks after treatment (group B), and 1 month after treatment (group C) groups in the case group. (B) Correlation analysis between the differences in the gut microbiota with differences in the levels of HPA axis hormones and inflammatory cytokines in the case group. (C) Correlation analysis of the effective (BE) and ineffective (BNE) groups *p < 0.05; **p < 0.01.
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