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Oral and intestinal microbiome of constipated cerebral palsy individuals that are using anticonvulsants

Abstract

Cerebral palsy (CP) Individuals present, in addition to motor damage, associated disorders such as epilepsy and, they use anticonvulsant drugs continuously. We could demonstrate the association between CP and gingivitis, in addition to a higher prevalence of caries and higher salivary osmolarity values. The prevalence of intestinal constipation in these individuals is high, ranging from 25% to 70%. In pathological conditions of stress and/or disease, intestinal dysbiosis can negatively influence intestinal physiology, leading to inappropriate indication to the microbiota-intestine-brain axis, with consequences for central nervous system functions and disease states. The objective of this study is to analyze the oral and intestinal microbiome of constipated CP individuals that are using anticonvulsants, in order to compare them to normal controls. Participants will be allocated in 3 groups: group (G1) will be composed of 10 children and adolescents with spastic type CP, with signs/symptoms of constipation, and use of anticonvulsant drugs; the group (G2) of 10 children and adolescents with a spastic type of CP, without signs/symptoms of intestinal constipation and using anticonvulsive drugs; and the control group (G3) by 20 normoreactive children and adolescents, matched by gender and age to G1 and G2 groups. Data regarding age, type of movement disorder, CP distribution, anticonvulsant use, effectiveness in controlling seizures, weight, height, body mass index, 3-day recall diary, global motor mobility, transfer to toilet seat, constipation and gingival evaluation will be collected. Saliva and stools samples will be collected and evaluated for microbial diversity by high performance sequencing of 16SrRNA. The sequences will be aligned for the construction of the phylogenetic tree. Alpha (Shannon and Simpson indices) and Beta-diversities based on the weighted and unweighted UNIFRAC phylogenetic index will be calculated. For all analyzes, the participant will be the unit of analysis. Parametric or non-parametric tests will be used after analysis of the results distribution. The frequency and abundance of OTUS at different taxonomic levels will be compared between groups. Associations between clinical, demographic and microbiological parameters will be analyzed through multiple linear and logistic regression models, adjusting for possible covariates. In these cases, the significance level of 5% will be set. Since the intestinal microbiota communicates with the brain via the gut-brain axis, understanding the intestinal microbiota in individuals with CP would not only target gingival inflammation and intestinal constipation but could possibly contribute to improving quality of life of these individuals, even modifying neurological symptoms such as seizure recurrence, behavioral, motor and cognitive problems.Keywords: Cerebral Palsy, Saliva, Stools, Epilepsy, Constipation, Gingival Inflammation, Oral Microbiome, Intestinal Microbiome. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FERREIRA, ANA CRISTINA FERNANDES MARIA; EVELOFF, RYAN J.; FREIRE, MARCELO; SANTOS, MARIA TERESA BOTTI RODRIGUES. The Impact of Oral-Gut Inflammation in Cerebral Palsy. FRONTIERS IN IMMUNOLOGY, v. 12, FEB 25 2021. Web of Science Citations: 0.
FERNANDES MARIA FERREIRA, ANA CRISTINA; ALVES MAYER, MARCIA PINTO; KAWAMOTO, DIONE; BOTTI RODRIGUES SANTOS, MARIA TERESA. Constipation, antiepileptic drugs, and gingivitis in children and adolescents with cerebral palsy. International Journal of Paediatric Dentistry, v. 29, n. 5, p. 635-641, SEP 2019. Web of Science Citations: 1.

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