Dataset Information

Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia

ABSTRACT: Familial dysautonomia (FD) is a rare genetic neurologic disorder caused by impaired neuronal development and progressive degeneration of both the peripheral and central nervous systems. FD is monogenic, with >99.4% of patients sharing an identical point mutation in the elongator acetyltransferase complex subunit 1 (ELP1) gene, providing a relatively simple genetic background in which to identify modifiable factors that influence pathology. Gastrointestinal symptoms and metabolic deficits are common among FD patients, which supports the hypothesis that the gut microbiome and metabolome are altered and dysfunctional compared to healthy individuals. Here we show significant differences in gut microbiome composition (16 S rRNA gene sequencing of stool samples) and NMR-based stool and serum metabolomes between a cohort of FD patients (~14% of patients worldwide) and their cohabitating, healthy relatives. We show that key observations in human subjects are recapitulated in a neuron-specific Elp1-deficient mouse model, and that cohousing mutant and littermate control mice ameliorates gut microbiome dysbiosis, improves deficits in gut transit, and reduces disease severity. Our results provide evidence that neurologic deficits in FD alter the structure and function of the gut microbiome, which shifts overall host metabolism to perpetuate further neurodegeneration.

INSTRUMENT(S): Nuclear Magnetic Resonance (NMR) -

SUBMITTER: Alexandra Cheney Stephanann Costello Jesse Peach

PROVIDER: MTBLS5138 | MetaboLights | 2022-12-06

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS5138	Other
	FILES	Other
	a_MTBLS5138_NMR_human_serum_metabolite_profiling.txt	Txt
	a_MTBLS5138_NMR_human_stool_metabolite_profiling.txt	Txt
	a_MTBLS5138_NMR_mouse_stool_metabolite_profiling.txt	Txt

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Publications

Gut microbiome dysbiosis drives metabolic dysfunction in Familial dysautonomia.

Cheney Alexandra M AM Costello Stephanann M SM Pinkham Nicholas V NV Waldum Annie A Broadaway Susan C SC Cotrina-Vidal Maria M Mergy Marc M Tripet Brian B Kominsky Douglas J DJ Grifka-Walk Heather M HM Kaufmann Horacio H Norcliffe-Kaufmann Lucy L Peach Jesse T JT Bothner Brian B Lefcort Frances F Copié Valérie V Walk Seth T ST

Nature communications 20230113 1

Familial dysautonomia (FD) is a rare genetic neurologic disorder caused by impaired neuronal development and progressive degeneration of both the peripheral and central nervous systems. FD is monogenic, with >99.4% of patients sharing an identical point mutation in the elongator acetyltransferase complex subunit 1 (ELP1) gene, providing a relatively simple genetic background in which to identify modifiable factors that influence pathology. Gastrointestinal symptoms and metabolic deficits are com ...[more]

PMID: 36639365

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