Study On The Correlation Between Intestinal Flora And Pathogenesis Of Infantile Spasms

Objective:To clarify the changes in the intestinal flora,inflammatory factors,and hypothalamus-pituitary-adrenal(HPA)axis hormones in children patients with infantile spasm(an intractable epilepsy syndrome whose pathogenesis may involve endocrine and immune factors,and the major influencing factor is the brain-gut axis),before and after treatment,and to explore the differences and correlation to provide a new reference for future exploration of the pathogenesis.Methods:Children patients with infantile spasms hospitalized in our hospital were involved in the Case Group,and the healthy children patients from 1 to 12 months were chosen as the Control Group.Serum and stool samples of children patients in the Case Group were collected before treatment,2 weeks after treatment,and 1 month after treatment.In addition,a single serum and stool sample of each healthy baby in the Control Group was collected.The serum samples were detected by flow cytometry(Cytometric Bead Array,CBA),enzyme-linked immunosorbent assay(ELISA),and chemiluminescent immunoassay(CLIA)to determine the levels of cytokines and HPA-related hormones.The collected stool samples were sequenced by 16 S r DNA,and the results were performed with bioinformatics analysis.Results:1.Through comparing,it can be found that(1)The levels of CRH,IL-2,IL-4,IL-6,and IL-17 in the Case Group before treatment were higher than those in the Control Group(P<0.05).(2)The quantity of Proteus,Bacillus and Morganella in the Case Group before treatment was more than those in the Control Group(P< 0.05),while the quantity of Sutterella,Sutterellaceae and Parasutterella were more than those in the Control Group(P< 0.05).(3)Through correlation analysis between the Case Group with a significant difference in flora before treatment and the levels of cytokines and HPA hormones,it was obtained that Lachnospiracea＿incertae＿sedis was positively correlated with CRH concentration(P<0.05).2.Through comparing the Case Group before treatment,2 weeks after treatment,and 1 month after treatment,it can be found that:(1)After treatment,the levels of CRH,ACTH,and COR decreased significantly(P<0.05);And,compared with those before treatment,the levels of IL-2,IL-4,IL-6 and IL-17 a in serum decreased after 1 month of treatment(P<0.05).(2)The quantity of Lachnospiracea＿incertae＿sedis in the Case Group before treatment was significantly higher than that after treatment(P<0.05);The quantity of Verrucomicrobia,Akkermansia,Clostridium XVIII and Ruminococcus2 in the Case Group after two weeks of treatment was higher than those after 1 month of treatment(P<0.05);The quantity of Sutterellaceae in the Case Group after 1 month of treatment was higher than that after 2 weeks of treatment(P<0.05).(3)By analyzing the correlation between flora,cytokine level,and HPA axis hormone level in different treatment periods,it was found that Sutterellaceae showed a positive correlation with CRH concentration in the Case Group after 1 month of treatment(P < 0.05),and a negative correlation with IL-2 and TNF-α(P<0.05).3.After two weeks of ACTH treatment,all patients were divided into the Effective Group and the Ineffective Group according to the relief of clinical symptoms:(1)The level of CRH and IFN-γ in the Effective Group was higher than that in the Ineffective Group(P<0.05).(2)In the Effective Group,the quantity of Clostridium XVIII,Alistipes,and Rikenellaceae increased(P<0.05);In the Ineffective Group,the quantity of Megamonas,Faecalibacterium,Ruminococcus,and Romboutsia increased(P< 0.05).(3)There was no correlation between the difference in the intestinal flora and the level of cytokines and HPA axis hormones in the two groups(P<0.05).Conclusion:1.There are differences in intestinal flora between infantile spasm children and healthy children.Lachnospiracea＿incertae＿sedis and Proteus may get involved in the onset of the disease.Also,the change of the dominant bacteria with the treatment may indicate that Verrucomicrobia,Akkermansia and Sutteraceae may be related to the improvement of children’s condition.This shows that targeting intestinal flora is expected to become a new auxiliary examination tool or treatment in future research and clinical application.2.In infantile spasms,the changes of some significantly different flora may affect the levels of some HPA axis hormones or cytokines.Lachnospiracea＿incertae＿sedis was positively correlated with blood CRH concentration before treatment,while Sutteraceae was negatively correlated with blood IL-2 and TNF-α concentration after treatment.This provides a new reference for the follow-up study on the mechanism of intestinal flora participating in the pathogenesis of infantile spasms.