Dataset Information

Distinct Gut Microbiota Composition and Functional Category in Children With Cerebral Palsy and Epilepsy.

ABSTRACT: Cerebral palsy (CP) and epilepsy are two interactive neurological diseases, and their clinical treatment can cause severe side-effects in children's development, especially when it involves long-term administration of antiepileptic drugs. Accumulating studies on the gut-brain axis indicated that the gut microbiota (GM), which participates in various neurological diseases, would provide a harmless therapeutic target for the treatment of CP and epilepsy. To explore the GM characteristics in children with both CP and epilepsy (CPE), we collected fecal samples from 25 CPE patients (CPE group) and 21 healthy children (Healthy group) for 16S rDNA sequencing. In this study, we discovered significantly higher microbial diversity in the CPE group compared to healthy group (P < 0.001). After selecting the top 15 most abundant genera in each group, we found significantly enriched Bifidobacterium, Streptococcus, Akkermansia, Enterococcus, Prevotella, Veillonella, Rothia, and Clostridium IV in the CPE group, and noticeably reduced Bacteroides, Faecalibacterium, Blautia, Ruminococcus, Roseburia, Anaerostipes, and Parasutterella. A GM co-occurrence network was also constructed, and negative correlations were discovered between Bacteroides and Lactobacillus (r = -0.768, P < 0.001, FDR < 0.001), as well as Intestinibacter and Bifidobacterium (r = -0.726, P < 0.001, FDR < 0.001). After KEGG annotation and functional enrichment, 24 functional categories exhibited different enrichment levels between the CPE and Healthy groups. The functions, associated with xenobiotics metabolism, immune system diseases, and neurodegenerative diseases, were enriched in the CPE group. Conversely, the functional categories related to the biosynthesis of secondary metabolites were reduced. Furthermore, the neurodegenerative diseases were mainly attributed to Streptococcus, while an increased risk of immune system diseases was associated with enriched Akkermansia in the CPE patients. Generally, this study characterized the GM in CPE patients, illustrated the microbial co-occurrence relationships, and detected the functional distributions of the bacteria.

SUBMITTER: Huang C

PROVIDER: S-EPMC6779726 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Distinct Gut Microbiota Composition and Functional Category in Children With Cerebral Palsy and Epilepsy.

Huang Congfu C Li Yinhu Y Feng Xin X Li Dongfang D Li Xiuyun X Ouyang Qiuxing Q Dai Wenkui W Wu Genfeng G Zhou Qian Q Wang Peiqin P Zhou Ke K Xu Ximing X Li Shuaicheng S Peng Yuanping Y

Frontiers in pediatrics 20191001

Cerebral palsy (CP) and epilepsy are two interactive neurological diseases, and their clinical treatment can cause severe side-effects in children's development, especially when it involves long-term administration of antiepileptic drugs. Accumulating studies on the gut-brain axis indicated that the gut microbiota (GM), which participates in various neurological diseases, would provide a harmless therapeutic target for the treatment of CP and epilepsy. To explore the GM characteristics in childr ...[more]

PMID: 31646147

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Project description:Gastrointestinal (GI) disorders are very common among children with cerebral palsy. Gut microbiota has been confirmed to maintain normal GI physiological function and further contributed to cerebral palsy through the gut-brain axis. Our study was to investigate the effect of dietary fiber combined with probiotics on functional constipated children with cerebral palsy. In total, 35 patient children were enrolled and divided into general diet group (n = 14) and liquid diet group (n = 21). All the participants received Compound Dietary Fiber (CDF) for 1 month and lactic acid-producing and butyric acid-producing probiotics for 6 months. After a 1-month intervention, the frequency of spontaneous and manual defecation, and Bristol score were all significantly improved (P < 0.001). The α-diversity of the gut microbiota was significantly increased after a 1-month intervention (P < 0.05), with a higher abundance of butyric acid-producing bacteria and a lower abundance of opportunistic pathogens (P < 0.05, FDR < 0.05). However, the impersistent effect of the 6-month intervention suggested the insufficient impact of intaking probiotics alone and the short duration of CDF intervention. Moreover, although the intervention had affected the constipation symptoms equally in cerebral palsy children with a general diet and liquid diet, the general diet group showed a greater and more durable change in gut microbiota and clinical phenotypes after intervention than the liquid diet group, which indicated that longer intervention time should be considered for liquid diet children. This study not only illustrated that supplementation of dietary fiber combined with probiotics can improve functional constipation in children with cerebral palsy, but also provides guidance for optimal intervention strategy for future studies, which will further benefit cerebral palsy children.Clinical trial registrationhttp://www.chictr.org.cn/showproj.aspx?proj=46902, identifier: ChiCTR1900028257.

Project description:Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies. Skeletal muscle biopsies from both the gracilis and semitendinosus were obtained during surgery for 20 pediatric subjects for affymetrix microarray analysis. We obtained a group of 10 patients undergoing medial hamstring lengthening in the cerebral palsy group and 10 patients undergoing ACL reconstruction with hamstring autograft in the control group. This provided 40 microarrays in 4 groups to analyze the effect of cerebral palsy and also differences between muscles.

Project description:ObjectiveThe objective of this study was to assess the rehabilitation status and factors associated with rehabilitation service utilisation among children with cerebral palsy (CP) in Bangladesh.Materials and methodsThis is a population-based surveillance study conducted among children with CP registered in the Bangladesh CP Register (BCPR), the first population-based register of children with CP aged <18 years (y) in Bangladesh. Children with CP were identified from the community using the key informant method and underwent a detailed neurodevelopmental assessment. Socio-demographic, clinical and rehabilitation status were documented. Unadjusted and adjusted analyses with a 95% confidence interval (CI) were used to identify potential predictors of rehabilitation service uptake.ResultsBetween January 2015 and December 2019, 2852 children with CP were registered in the BCPR (mean (standard deviation, SD) age: 7 y 8 months (mo) (4 y 7 mo), 38.5% female). Of these, 50.2% had received rehabilitation services; physiotherapy was the most common type of service (90.0%). The mean (SD) age at commencement of rehabilitation services was 3 y 10 mo (3 y 1 mo). The odds of not receiving rehabilitation was significantly higher among female children (adjusted odds ratio (aOR) 1.3 [95% CI: 1.0-1.7], children whose mothers were illiterate and primary level completed (aOR 2.1 [95% CI: 1.4-3.1] and aOR 1.5 [95% CI: 1.1-2.1], respectively), fathers were illiterate (aOR 1.9 [95% CI: 1.3-2.8]), had a monthly family income ~US$ 59-118 (aOR: 1.8 [95% CI: 1.2-2.6]), had hearing impairment (aOR: 2.3 [95% CI: 1.5-3.5]) and motor severity (i.e. Gross Motor Function Classification System level III (aOR: 0.6 [95% CI: 0.3-0.9]) and level V (aOR: 0.4 [95% CI: 0.2-0.7])).ConclusionsRehabilitation status was poor among the majority of the children with CP in the BCPR cohort, limiting their opportunities for functional improvement. A community-based rehabilitation model focusing on socio-demographic and clinical characteristics should be a public health priority in Bangladesh.

Project description:Background: Oral-gut inflammation has an impact on overall health, placing subjects at risk to acquire chronic conditions and infections. Due to neuromotor disturbances, and medication intake, cerebral palsy (CP) subjects present intestinal constipation, impacting their quality of life (QOL). We aimed to investigate how oral inflammatory levels predicted gut phenotypes and response to therapy. Methods: A total of 93 subjects aging from 5 to 17 years were included in the study, and assigned into one of the 4 groups: CP with constipation (G1, n = 30), CP without constipation (G2, n = 33), and controls without CP with constipation (G3, n = 07) and without CP and without constipation (G4, n = 23). In addition to characterizing subjects' clinical demographics, medication intake, disease severity levels, salivary cytokine levels [TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10], and Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD). Statistical significance was evaluated by Shapiro-Wilks, Student's T-Test, ANOVA, and ANCOVA analysis. Results: Salivary proinflammatory cytokines were highly correlated with the severe form of gut constipation in G1 (P < 0.001), and out of all cytokines IL-1β levels demonstrated highest correlation with all gut constipation (P < 0.05). A significant relationship was found between the type of medication, in which subjects taking Gamma-Aminobutyric Acid (GABA) and GABA+ (GABA in association with other medication) were more likely to be constipated than the other groups (P < 0.01). Cleary salivary inflammatory levels and gut constipation were correlated, and impacted QOL of CP subjects. G1 presented a lower QOL mean score of CPCHILD (49.0 ± 13.1) compared to G2 (71.5 ± 16.7), when compared to G3 (88.9 ± 7.5), and G4 (95.5 ± 5.0) (P < 0.01). We accounted for gingival bleeding as a cofounder of oral inflammation, and here were no differences among groups regarding gender (P = 0.332) and age (P = 0.292). Conclusions: Collectively, the results suggest that saliva inflammatory levels were linked to gut constipation, and that the clinical impact of medications that controlled gut was reliably monitored via oral cytokine levels, providing reliable and non-invasive information in precision diagnostics.

Dataset Information

Distinct Gut Microbiota Composition and Functional Category in Children With Cerebral Palsy and Epilepsy.

Publications

Distinct Gut Microbiota Composition and Functional Category in Children With Cerebral Palsy and Epilepsy.

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