Exploratory metabolomic profiling in migraine with PFO reveals dysregulated pathways and highlights indoleacrylic acid.

Overview

1. Department of Cardiology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610031, China
2. Structural Heart Disease Committee, Sichuan Association of Rehabilitation Medicine, Chengdu 610031, China
3. Ultrasound Medicine and Computational Cardiology Key Laboratory of Sichuan Province, Chengdu 610031, China
4. Department of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610031, China
5. WangJiang Hospital, Sichuan University, Chengdu 610031, China
6. Key Laboratory of Ultrasound in Cardiac Electrophysiology and Biomechanics of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610031, China
7. Department of Neurology, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610031, China
8. Department of Cardiology, Sichuan Provincial People’s Hospital, North Sichuan Medical College, Nanchong 637000, China

Abstract

Patent foramen ovale (PFO) is increasingly linked to migraine, yet its systemic metabolic effects remain unclear. Using untargeted metabolomics, we analyzed arterial and venous plasma from migraine patients with PFO (PFO-M, n = 30) and venous plasma from healthy controls (n = 17). We identified 211 differentially expressed metabolites and multiple pathways involving branched-chain amino acids, neurosteroids, and tryptophan metabolism. The gut microbiota-derived metabolite indoleacrylic acid (IA) was inversely associated with migraine severity and was reduced in female PFO-M patients. In an independent cohort (n = 220), lower IA remained negatively associated with PFO-M (OR = 0.97, 95% CI 0.96–0.98), and the combination of IA and hs-CRP improved discriminative performance compared with either marker alone (AUC = 0.722). Together, these exploratory findings suggest systemic metabolic alterations in PFO-comorbid migraine and highlight IA as a candidate metabolic feature, supporting a potential role of gut-brain axis dysregulation.

Reproduced under the paper's license (CC BY), from the paper cited above.

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The raw metabolomics data generated in this study have been deposited in the MetaboLights: MTBLS13630 and are publicly available as of the date of publication.

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Any additional information is available from the lead contact upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 2, 28 September 2026

• Authors: added Cong Lu (0000-0002-1193-2060); removed Cong Lu

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 2 keywords, 3 funders, 49 references.

Cite

This paper

Luo, T., Xi, Q., Wang, Q., Wang, Y., Huang, R., Wang, X., Zhou, Y., Huang, H., Zeng, J., & Lu, C. (2026). Exploratory metabolomic profiling in migraine with PFO reveals dysregulated pathways and highlights indoleacrylic acid. iScience, 29(5), 115587. https://doi.org/10.1016/j.isci.2026.115587

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