PRJNA785599
A comprehensiveand integrativeanalysis of systemic metabolic dysfunction and gut microbiome dysbiosis in Familial dysautonomia
Familial dysautonomia, FD, is a rare, monogenic, and debilitating disease that impacts the development and maturation of the peripheral and central nervous systems due to mutations in the Elongator subunit ELP1. This patient population represents a unique opportunity to not only evaluate the microbiomes role in the onset and progression of FD but its impact in more complex neurodegenerative diseases, such as Parkinsons and Alzheimers Disease. Here, we enrolled FD patients and a cohabitating relative. Paired blood and stool samples were obtained with consent and NMR based metabolomics was performed to compare metabolite levels and possibly altered metabolic pathways. In parallel, 16S rRNA gene sequencing was performed on fecal samples to characterize gut microbiome diversity. Elevated concentrations of choline was detected in FD patient stool. The metabolic and gut microbiome analyses, both separately and integrated, identified valuable markers that associate with known clinical phenotypes of FD patients and disease severity. Overall, our study provides a framework for deciphering the gut microbial and metabolic gut brain liver axis impairments in FD and potentially for other related neurological disorders.