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
en 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
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Síndrome de Rett
/
Progresión de la Enfermedad
/
Metaboloma
/
Microbioma Gastrointestinal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Commun Biol
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos