Intestinal Dysbiosis as a component of pathophysiology in succinic semialdehyde dehydrogenase deficiency (SSADHD).
Mol Genet Metab
; 135(1): 42-46, 2022 01.
Article
em En
| MEDLINE
| ID: mdl-34896003
ABSTRACT
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited inborn error of the γ-aminobutyric acid (GABA) metabolism pathway. It results from mutations in the ALDH5A1 gene leading to elevated GABA, γ-hydroxybutyric acid (GHB), succinic semialdehyde (SSA), decreased glutamine and alterations in several other metabolites. The phenotype includes developmental and cognitive delays, hypotonia, seizures, neuropsychiatric morbidity and other nervous system pathologies. The composition of the intestinal flora of patients with SSADHD has not been characterized, and dysbiosis of the gut microbiome may unveil novel treatment paradigms. We investigated the gut microbiome in SSADHD using 16S ribosomal DNA sequencing and unmasked evidence of dysbiosis in both aldh5a1-deficient mice and patients with SSADHD. In the murine model, there was a reduction in α-diversity measurements, and there were 4 phyla, 3 classes, 5 orders, 9 families, and 15 genera that differed, with a total of 17 predicted metabolic pathways altered. In patients, there were changes in Fusobacterium, 3 classes, 4 orders, 11 families, and a predicted alteration in genes associated with the digestive system. We believe this is the first evaluation of microbiome structure in an IEM with a neurometabolic phenotype that is not treated dietarily.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Disbiose
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Erros Inatos do Metabolismo dos Aminoácidos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Child
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article