ORIGINAL RESEARCH article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1696763
This article is part of the Research TopicThe Gut-Brain Axis: Microbiota-Driven Immune Modulation and its Impact on Neurological HealthView all 11 articles
Sex differences in abnormal gluten response and predictors of gluten sensitivity in patients with schizophrenia
Provisionally accepted
- 1Uniwersytet Medyczny w Lublinie, Lublin, Poland
- 2Katolicki Uniwersytet Lubelski Jana Pawla II, Lublin, Poland
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Immune-inflammatory dysregulations are linked to shifts in specific gut microbiota genera, underscoring the importance of the gut–brain connection in schizophrenia (SZ). However, the immune-inflammatory aspects of sex differences in SZ remain largely unexplored. The aims of this study were: (1) to identify sex-related differences in inflammatory response, intestinal biomarkers, and gluten sensitivity in SZ; and (2) to determine potential factors underlying variability in the immune response to gluten in this population. A total of 102 individuals with SZ and 60 healthy controls (HC) were included in the study. Elevated titers of anti-gliadin (AGA) IgA were found in 26% of individuals with SZ compared to 22% of HC, and elevated AGA IgG in 30% of SZ patients compared to 20% of HC. IgG levels were higher in men than in women, regardless of health status. Significant differences in the levels of AGA IgG and deamidated gliadin (dGP) IgG were observed between men and women with SZ, with higher concentrations detected in men. Factors differentiating patients with positive AGA IgA antibodies included tissue transglutaminase (tTG) IgA levels, high sensitivity C-reactive protein (hs-CRP) levels, and age. Factors associated with positive AGA IgG antibodies included dGP and anti-saccharomyces cerevisiae (ASCA) antibodies levels, negative symptoms of SZ, and age of onset. This is the first study to examine sex-related differences and illness stage in the immune response to gluten among in SZ. Stronger inflammatory responses were found in males, suggesting sex-related disparities in gluten-related immune activation. These findings highlight a complex interplay between hormones, immune function, intestinal barrier integrity, and psychiatric symptoms. Further longitudinal research is needed to clarify these mechanisms and their clinical significance.
Keywords: inflammation-dependent psychiatric disorders, gluten, Cytokines, low-grade inflammation, food immune reactivity
Received: 01 Sep 2025; Accepted: 15 Oct 2025.
Copyright: © 2025 Dzikowski, Rog, Juchnowicz, Rymuszka and Karakula-Juchnowicz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Joanna Rog, rog.joann@gmail.com
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