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Intestinal Dysbiosis as a component of pathophysiology in succinic semialdehyde dehydrogenase deficiency (SSADHD).
Kirby, Trevor O; Shi, Xutong; Walters, Dana; Roullet, Jean-Baptiste; Gibson, K Michael.
Afiliação
  • Kirby TO; Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA.
  • Shi X; Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA.
  • Walters D; Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA.
  • Roullet JB; Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA.
  • Gibson KM; Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA. Electronic address: mike.gibson@wsu.edu.
Mol Genet Metab ; 135(1): 42-46, 2022 01.
Article em En | MEDLINE | ID: mdl-34896003
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Disbiose / Erros Inatos do Metabolismo dos Aminoácidos Tipo de estudo: Prognostic_studies Limite: Animals / Child / Humans Idioma: En Revista: Mol Genet Metab Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / METABOLISMO Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Disbiose / Erros Inatos do Metabolismo dos Aminoácidos Tipo de estudo: Prognostic_studies Limite: Animals / Child / Humans Idioma: En Revista: Mol Genet Metab Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA / METABOLISMO Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos