Sex disparate gut microbiome and metabolome perturbations precede disease progression in a mouse model of Rett syndrome.
Commun Biol
; 4(1): 1408, 2021 12 16.
Article
em En
| MEDLINE
| ID: mdl-34916612
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 MECP2, the intermediate molecular pathways of progressive disease phenotypes are unknown. Mecp2 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 Mecp2e1 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 Mecp2 animal models.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Rett
/
Progressão da Doença
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Metaboloma
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Microbioma Gastrointestinal
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Commun Biol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos