AccScience Publishing / BH / Online First / DOI: 10.36922/BH026050005
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REVIEW ARTICLE

Gluten-related disorders and brain–heart interactions: Pathophysiological links, clinical manifestations, and translational implications

Giustino Varrassi1,2* ,  Y Van Tran3 ,  Phong Van Pham3 ,  Ameen Abdulhasan Al Alwany2 ,  Dariusz Myrcik4 ,  Annalisa Caruso5 ,  Matteo Luigi Giuseppe Leoni6
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1 Department of Research, Fondazione Paolo Procacci, Rome, Italy
2 Department of Research and Cardiolgy, College of Medicine, University of Baghdad, Baghdad, Iraq
3 Department of Anesthesiology, Tam Anh General hospital, Ho Chi Minh City, Vietnam
4 Department of Propaedeutics of Internal Diseases and Emergency Medicine, Medical University of Silesia, Katowice, Silesian Voivodeship, Poland
5 Department of Surgery, Azienda Socio-Sanitaria Territoriale di Lodi, Lodi, Italy
6 Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
Brain & Heart, 026050005 https://doi.org/10.36922/BH026050005
Received: 26 January 2026 | Revised: 5 February 2026 | Accepted: 24 February 2026 | Published online: 17 April 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Gluten-related disorders (GRDs), including celiac disease, non-celiac gluten sensitivity, and wheat allergy, are increasingly recognized as systemic immune-mediated conditions with clinically significant neurological, psychiatric, and cardiovascular manifestations that extend beyond their classical gastrointestinal phenotype. Epidemiological and clinical evidence have linked GRDs to gluten ataxia, peripheral neuropathy, cognitive dysfunction, affective disorders, increased cardiovascular risk, and autonomic dysregulation. Mechanistic research implicates convergent pathways involving intestinal barrier disruption, systemic immune activation, autoantibody cross-reactivity, blood–brain barrier dysfunction, and endothelial injury mediated by chronic inflammation. This narrative review synthesizes current evidence on the pathophysiology of brain–heart involvement in GRDs through the lens of the gut– brain–heart axis, integrating neuroimmune, autonomic, and vascular mechanisms. We examine the potential for reversibility of selected neurocardiac manifestations through dietary and adjunctive interventions, alongside critical knowledge gaps in mechanistic understanding, biomarker development, and therapeutic targeting. A systems-level framework for understanding GRDs may improve diagnostic recognition, cardiovascular and neurological risk stratification, and inform more integrated clinical management strategies.

Keywords
Gluten-related disorders
Celiac disease
Gut–brain–heart axis
Neuroimmune interactions
Autonomic dysfunction
Cardiovascular involvement
Blood–brain barrier dysfunction
Funding
This research received no external funding.
Conflict of interest
Giustino Varrassi and Matteo Luigi Giuseppe Leoni are Editorial Board Member and Guest Editor of this journal, but were not in any way involved in the editorial peer-review process conducted for this paper, directly or indirectly. The authors declare no conflicts of interest.
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Brain & Heart, Electronic ISSN: 2972-4139 Published by AccScience Publishing
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