Neier et al. Communications Biology Supplementary Data

Supplementary data for paper published in Communications Biology titled "Sex disparate gut microbiome and metabolome perturbations precede disease progression in a mouse model of Rett syndrome." <b></b><br>Abstract: Rett syndrome (RTT) is a regressive neurodevelopmental disorder in girls, characterized by multisystem complications including gut dysbiosis and altered metabolism. While RTT is known to be caused by mutations in the X-linked gene <i>MECP2</i>, the intermediate molecular pathways of progressive disease phenotypes are unknown. <i>Mecp2</i> deficient rodents used to model RTT pathophysiology in most prior studies have been male. Thus, we utilized a patient-relevant mouse model of RTT to longitudinally profile the gut microbiome and metabolome across disease progression in both sexes. Fecal metabolites were altered in <i>Mecp2e1</i> mutant females before onset of neuromotor phenotypes and correlated with lipid deficiencies in brain, results not observed in males. Females also displayed altered gut microbial communities and an inflammatory profile that were more consistent with RTT patients than males. These findings identify new molecular pathways of RTT disease progression and demonstrate the relevance of further study in female <i>Mecp2</i> animal models.