Altered Intestinal Permeability Biomarkers in Schizophrenia: A Possible Link with Subclinical Inflammation

Author:

Gokulakrishnan Kuppan1ORCID,Nikhil Joyappa1,VS Sreeraj2,Holla Bharath3,Thirumoorthy Chinnasamy1,Sandhya Narasimhan1,Nichenametla Sonika2,Pathak Harsh2,Shivakumar Venkataram3ORCID,Debnath Monojit4,Venkatasubramanian Ganesan2,Varambally Shivarama23ORCID

Affiliation:

1. Department of Neurochemistry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India

2. Department of Psychiatry, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka India

3. Department of Integrative Medicine, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India

4. Department of Human Genetics, National Institute of Mental Health and Neuro Sciences, Bengaluru, Karnataka, India

Abstract

Background and Purpose Emerging studies have shown that gut-derived endotoxins might play a role in intestinal and systemic inflammation. Although the significance of intestinal permeability in modulating the pathogenesis of Schizophrenia (SCZ) is recognized, not much data on the specific role of intestinal permeability biomarkers, viz., zonulin, lipopolysaccharide-binding protein (LBP), and intestinal alkaline phosphatase (IAP) in SCZ is available. Therefore, we measured the plasma levels of zonulin, LBP, and IAP and its correlation with neutrophil-to-lymphocyte ratio (NLR); a marker of systemic inflammation in patients with SCZ. Methods We recruited 60 individuals, patients with SCZ ( n = 40) and healthy controls ( n = 20), from a large tertiary neuropsychiatry center. Plasma levels of zonulin, IAP, and LBP were quantified by enzyme-linked immunosorbent assay. Results Plasma levels of both LBP and zonulin were significantly increased ( P <0.05), whereas the IAP levels ( P <0.05) were significantly decreased in patients with SCZ compared to healthy controls. Pearson correlation analysis revealed that zonulin and LBP had a significant positive correlation with NLR, and IAP negatively correlated with NLR. Individuals with SCZ had higher independent odds of zonulin [odds ratio (OR): 10.32, 95% CI: 1.85–57.12], LBP [OR: 1.039, 95% CI: 1.02–1.07], and IAP [OR: 0.643, 95% CI: 0.471–0.879], even after adjusting for potential confounders. Conclusion Our study demonstrates an association of zonulin, LBP, and IAP in Asian Indian SCZ patients and correlates with NLR. Our results indicate that low-grade inflammation induced by metabolic endotoxemia might be implicated in the pathoetiology of SCZ.

Publisher

SAGE Publications

Subject

General Neuroscience

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