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

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.

Association of Blast Exposure in Military Breaching with Intestinal Permeability Blood Biomarkers Associated with Leaky Gut

“…Zonulin is a known physiological modulator of intercellular tight junctions synthesized within intestinal and liver cells [ 17 ] that modulates the permeability of tight junctions between cells of the wall of the digestive tract. Zonulin has been used as an IP biomarker for autoimmune diseases such as inflammatory bowel disease (Crohn’s disease [ 31 ]), as well as multiple sclerosis [ 32 ] and Schizophrenia [ 33 ]. In the present study, the plasma level of Zonulin was significantly increased at 1 h and 16 h post blast exposure, indicating that blast may contribute to the impairment of the gut barrier in the paracellular pathway ( Figure 3 and Table 2 ), which was further supported by elevated bacteria alpha diversity in the blood transcriptome ( Figure 2 b and Table 2 ).…”

“…Zonulin is a known physiological modulator of intercellular tight junctions synthesized within intestinal and liver cells [17] that modulates the permeability of tight junctions between cells of the wall of the digestive tract. Zonulin has been used as an IP biomarker for autoimmune diseases such as inflammatory bowel disease (Crohn's disease [31]), as well as multiple sclerosis [32] and Schizophrenia [33].…”

Increased IgA-mediated responses to the gut paracellular pathway and blood–brain barrier proteins predict delirium due to hip fracture in older adults

“…Interestingly, the current immune findings in delirium partly overlap with previous findings in schizophrenia. Thus, in schizophrenia, several studies reported significant associations with increased bacterial translocation ( 78 – 80 ), breakdown of transcellular and paracellular tight/adherens junction barriers ( 23 , 81 , 82 ), as well as the BBB ( 24 , 83 ). Moreover, our study demonstrated a significant association between increased levels of IgA in P. gingivalis , H. pylori , and CDT (and their z composite score) and delirium severity.…”

Serum trimethylamine N‐oxide and lipopolysaccharide binding protein levels among children diagnosed with autism spectrum disorder

“…In a different study on the subject, plasma levels of both LBP and zonulin are significantly increased, and plasma intestinal alkaline phosphatase levels are found decreased among patients with schizophrenia. The authors suggest that metabolic endotoxemia-induced low-grade inflammation might play a role in the etiology of schizophrenia (Gokulakrishnan et al, 2022). For ASD, intestinal and blood-brain barrier (BBB) dysfunction because of permeability changes has gained interest, too.…”