Abstract
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder affecting 1 in 10,000 live female births. Changes in microbiota composition, as observed in other neurological disorders such as autism spectrum disorders, may account for several symptoms typically associated with RTT. We studied the relationship between disease phenotypes and microbiome by analyzing diet, gut microbiota, and short-chain fatty acid (SCFA) production. We enrolled eight RTT patients and 10 age- and sex-matched healthy women, all without dietary restrictions. The microbiota was characterized by 16S rRNA gene sequencing, and SCFAs concentration was determined by gas chromatographic analysis. The RTT microbiota showed a lower α diversity, an enrichment in Bacteroidaceae, Clostridium spp., and Sutterella spp., and a slight depletion in Ruminococcaceae. Fecal SCFA concentrations were similar, but RTT samples showed slightly higher concentrations of butyrate and propionate, and significant higher levels in branched-chain fatty acids. Daily caloric intake was similar in the two groups, but macronutrient analysis showed a higher protein content in RTT diets. Microbial function prediction suggested in RTT subjects an increased number of microbial genes encoding for propionate and butyrate, and amino acid metabolism. A full understanding of these critical features could offer new, specific strategies for managing RTT-associated symptoms, such as dietary intervention or pre/probiotic supplementation.
Highlights
Rett syndrome (RTT; OMIM 312750) is an X-linked neurodevelopmental disorder and one of the most common causes of intellectual disability in females. 90%–95% percent of cases are associated with mutations in the MECP2 (Methyl CpG Binding Protein 2) gene, encoding a chromatin-associated protein that can both activate and repress transcription [1,2]
Our study showed changes in the intestinal microbial profile that could affect comorbidities OasusorcsiatuteddywsithhoRwTeTdsychndarnogmees. iTnhitshies itnhetessetcionnadl mstuicdryobinivaelsptirgoafitilnegtthhaetRcToTumldicarfofbeicotmceoamnodrtbhiedities assocfiiarstet,dtowoituhr RkTnoTwslyedngder,otmhaet. cTohmispaisretdhedsieetcaoryndinstatukedsy, ainvthersotpigoamteintrgicthmeeaRsTuTremeicnrtos,bmioimcroebaianld the first, ptorofoiulers,kanndowfelceadl gSCe,FAthcaotnccoemntrpaatiroends.dietary intakes, anthropometric measurements, microbial profiles, aOnudrfedcaatlaSsCuFgAgesctonthcaetntthraetiRoTnTs. microbial population is reduced in richness and evenness
Our cohort was older than the patients enrolled by Strati et al, and bifidobacteria abundance is inversely correlated with age, and strongly dependent on diet [31,32,33]
Summary
Rett syndrome (RTT; OMIM 312750) is an X-linked neurodevelopmental disorder and one of the most common causes of intellectual disability in females. 90%–95% percent of cases are associated with mutations in the MECP2 (Methyl CpG Binding Protein 2) gene, encoding a chromatin-associated protein that can both activate and repress transcription [1,2]. 90%–95% percent of cases are associated with mutations in the MECP2 (Methyl CpG Binding Protein 2) gene, encoding a chromatin-associated protein that can both activate and repress transcription [1,2]. RTT is characterized by 6–18 months of apparently normal neurodevelopment followed by neurological regression [3]. Neurological features such as microcephaly, stereotyped hand movements, behavioral problems, seizures, and dyspraxia are the main characteristics of RTT, but respiratory abnormalities and gastrointestinal dysfunctions are commonly reported [4]. RTT female patients, who are generally heterozygous for MECP2 gene mutations, have variable MeCP2 expression (and varying phenotypes) due to random X-inactivation patterns. Of the two MeCP2 protein isoforms generated by alternative splicing of the MECP2 gene (MeCP2E1 and MeCP2E2), MeCP2E1 is the major isoform in the brain in both mice and humans, and its deficiency is responsible for the phenotype [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
