Rett syndrome 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. RTT is characterized by 6–18 months of apparently normal neurodevelopment followed by neurological regression. 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 also commonly reported . RTT female patients, who are generally heterozygous for MECP2 gene mutations, have variable MeCP2 expression (and varying phenotypes) due to random X-inactivation patterns. Males who are null for MeCP2 expression are more severely affected and often do not survive birth. 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.

Recent results revealed the occurrence of an intestinal sub-inflammatory status in RTT and a concomitant alteration of relative abundances of bacterial and fungal components in RTT subjects compared with healthy controls. Changes in microbiota composition, as observed in other neurological disorders such as autism spectrum disorders (ASD), may contribute to several typical symptoms associated with RTT syndrome.

It has been shown that a dysbiotic gut microbiota may affect the function of the nervous system. Putative mechanisms by which bacterial products affect central and enteric nervous systems are via cytokine release from mucosal immune cells, via the release of gut hormones from enteroendocrine cells, or via afferent neural pathways, including the vagus nerve. This communication is bidirectional: microbiota influences CNS function, and the CNS influences the microbiota composition through its effects on the gastrointestinal tract. Microbial short chain fatty acids (SCFAs), primarily acetate, butyrate, and propionate, are key players in this landscape. Their production relies on various factors such as the microbial species inhabiting the gut, the substrate source and availability, and the gut transit time.

Now that we know about Rett Syndrome and the microbial key players responsible for developing symptoms. Lets now explore a dataset from Bioproject. We’ll download this data and prepare it for running the pipeline on T-Bioinfo Server. 

Steps to download dataset from Bioproject

Click on the link to access the data on Rett Syndrome: https://www.omicsdi.org/dataset/omics_ena_project/PRJNA355083

Next, click on the “Access Data” button which will redirect you to the bioproject https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA355083.

You can run the demo pipeline on the T-Bioinfo Server to learn the flow of steps in the pipeline and visualize the results obtained: https://server.t-bio.info/pipelinesmetagenomicsqiime2/demopipelines/demo-rett-syndrome

To get more insights about the project, run the pipelines and learn to interpret results, you can visit the example project on the OmicsLogic Learn Portal: https://learn.omicslogic.com/courses/course/project-19-effect-of-non-antibiotics-and-rett-syndrome