Gut metabolites identified in cerebrospinal fluid of genetic interferonopathy support gut–brain endothelial dysfunction

Dale, RC; Elbourne, M; Hofer, MJ; Patel, S; Mohammad, S; Han, VX; Yu, J; Fu, S; D'Silva, A; Farrar, MA; Bandodkar, S; Yan, JJ

Gut metabolites identified in cerebrospinal fluid of genetic interferonopathy support gut–brain endothelial dysfunction

Dale, RC Elbourne, M Hofer, MJ Patel, S Mohammad, S Han, VX Yu, J Fu, S D'Silva, A Farrar, MA Bandodkar, S Yan, JJ

Permalink

Publisher:: Wiley
Publication Type:: Journal Article
Citation:: Clinical & Translational Immunology, 2026, 15, (2)
Issue Date:: 2026-02

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Published versionAdobe PDF (380.23 kB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Dale, RC
dc.contributor.author	Elbourne, M
dc.contributor.author	Hofer, MJ
dc.contributor.author	Patel, S
dc.contributor.author	Mohammad, S
dc.contributor.author	Han, VX
dc.contributor.author	Yu, J
dc.contributor.author	Fu, S
dc.contributor.author	D'Silva, A
dc.contributor.author	Farrar, MA
dc.contributor.author	Bandodkar, S
dc.contributor.author	Yan, JJ
dc.date.accessioned	2026-02-20T05:23:14Z
dc.date.available	2026-02-20T05:23:14Z
dc.date.issued	2026-02
dc.identifier.citation	Clinical & Translational Immunology, 2026, 15, (2)
dc.identifier.issn	2050-0068
dc.identifier.issn	2050-0068
dc.identifier.uri	http://hdl.handle.net/10453/193673
dc.description.abstract	<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objective</jats:title> <jats:p>Aicardi–Goutières syndrome (AGS) is a rare genetic interferonopathy because of aberrant DNA or RNA metabolism with secondary host anti‐viral (interferon) activation. This metabolomics study aimed to improve the biological understanding of AGS and explore potential biomarkers.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We performed untargeted cerebrospinal fluid (CSF) metabolomics using a UPLC‐Q‐Exactive‐HFx Mass Spectrometry of 10 genetically confirmed AGS patients (8 males, mean 4.8 years, range 0.2–16.5) and age‐sex matched controls. Metabolites were then quantified and validated using UHPLC‐QqQ‐MS/MS in CSF and serum.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> We identified expected elevated inflammatory metabolites (neopterin and kynurenine) and unexpected elevated gut microbe metabolites in CSF samples: Indole, p‐Cresol, γ‐Butyrobetaine and N‐Butyryl‐L‐homoserine lactone (all <jats:italic>P</jats:italic> <jats:sub>FDR</jats:sub> < 0.05). Using a targeted assay, we confirmed elevation of these metabolites in CSF, and also in the serum of patients with AGS (all <jats:italic>P</jats:italic> < 0.01). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>Our findings suggest gut microbe metabolite leakage traversing the gut–blood–brain barrier in AGS, potentially because of endothelial dysfunction.</jats:p> </jats:sec>
dc.language	en
dc.publisher	Wiley
dc.relation	University of Technology Sydney
dc.relation.ispartof	Clinical & Translational Immunology
dc.relation.isbasedon	10.1002/cti2.70074
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1107 Immunology, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	3204 Immunology
dc.title	Gut metabolites identified in cerebrospinal fluid of genetic interferonopathy support gut–brain endothelial dysfunction
dc.type	Journal Article
utslib.citation.volume	15
utslib.for	1107 Immunology
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-02-20T05:23:12Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	15
utslib.citation.issue	2

Abstract:

Abstract Objective Aicardi–Goutières syndrome (AGS) is a rare genetic interferonopathy because of aberrant DNA or RNA metabolism with secondary host anti‐viral (interferon) activation. This metabolomics study aimed to improve the biological understanding of AGS and explore potential biomarkers. Methods We performed untargeted cerebrospinal fluid (CSF) metabolomics using a UPLC‐Q‐Exactive‐HFx Mass Spectrometry of 10 genetically confirmed AGS patients (8 males, mean 4.8 years, range 0.2–16.5) and age‐sex matched controls. Metabolites were then quantified and validated using UHPLC‐QqQ‐MS/MS in CSF and serum. Results We identified expected elevated inflammatory metabolites (neopterin and kynurenine) and unexpected elevated gut microbe metabolites in CSF samples: Indole, p‐Cresol, γ‐Butyrobetaine and N‐Butyryl‐L‐homoserine lactone (all P FDR < 0.05). Using a targeted assay, we confirmed elevation of these metabolites in CSF, and also in the serum of patients with AGS (all P < 0.01). Conclusion Our findings suggest gut microbe metabolite leakage traversing the gut–blood–brain barrier in AGS, potentially because of endothelial dysfunction.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/193673